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    1ํ˜• ๋‹น๋‡จ๋ณ‘ ์ฒญ์†Œ๋…„์—์„œ ์ผ์ค‘ ํ˜ˆ์•• ๋ณ€๋™์ด ๋ฏธ์„ธํ˜ˆ๊ด€ ํ•ฉ๋ณ‘์ฆ ๋ฐœ์ƒ์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ) -- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์˜๊ณผ๋Œ€ํ•™ ์˜ํ•™๊ณผ, 2021. 2. ์‹ ์ถฉํ˜ธ.The effects of circadian blood pressure (BP) alterations on the development and progression of microvascular complications remain to be determined in type 1 diabetes (T1DM). This study evaluated the effects of circadian BP alterations such as non-dipper hypertension with development of microvascular complications during follow-up of patients with childhood-onset T1DM. We investigated the medical records of 81 pediatric patients (33 males and 48 females) with T1DM who had received 24-h ambulatory BP monitoring (ABPM) between January 2009 and February 2010 at Seoul National University Childrenโ€™s Hospital. The effects of circadian BP alterations such as non-dipper hypertension on the development of microvascular complications over 8 years of follow-up were evaluated after adjusting for glycemic control and the duration of T1DM. The mean ages at T1DM diagnosis and ABPM evaluation were 8.0 ยฑ 3.9 and 15.6 ยฑ 2.4 years, respectively. Hypertension (daytime, nighttime, and/or 24-h mean hypertension) was present in 42 (51.9%) patients. The results of 24-h ABPM were categorized into three circadian BP groups: dipper (n = 30, 37.0%), non-dipper normotension (n = 18, 22.2%), and non-dipper hypertension (n = 33, 40.7%). During the 8 years of follow-up after ABPM, microvascular complications occurred in eight patients (diabetic retinopathy [DR] in six, microalbuminuria in three, and both in one), of whom seven had non-dipper BP. Nighttime diastolic BP (standard deviation score: 1.29 ยฑ 1.06 vs. 1.85 ยฑ 0.46), nighttime mean arterial pressure (1.28 ยฑ 1.26 vs. 1.98 ยฑ 0.57), and the hemoglobin A1c level (8.5 ยฑ 1.0% vs. 10.1 ยฑ 0.7%) were significantly higher in patients with DR than in those without DR (p < 0.05 for all). Daytime or nighttime BP and presence of dipper BP were not related to microvascular complications, but diabetic microvascular complications were more likely to occur in patients with an older age at diagnosis and higher hemoglobin A1c level. In addition, the risk of developing DR was significantly higher in those of adolescent age at diagnosis. The proportion of patients with DR was significantly higher in those with non-dipper hypertension (83.3%) compared with dipper and non-dipper normotension (0% and 16.7%, respectively; p = 0.021). As a predictor of microvascular complications, the hazard ratio of non-dipper hypertension was evaluated using Cox proportional hazards regression analysis; however, the results were not significant. Glycemic control rather than non-dipper hypertension in childhood is the predominant factor determining DR in T1DM patients. Further research is needed to evaluate the relationship between non-dipper hypertension and microvascular complications.1ํ˜• ๋‹น๋‡จ ํ™˜์ž์—์„œ ๋ฏธ์„ธํ˜ˆ๊ด€ ํ•ฉ๋ณ‘์ฆ์˜ ๋ฐœ์ƒ๊ณผ ์ง„ํ–‰์— 24์‹œ๊ฐ„ ํ˜ˆ์•• ๋ณ€ํ™”๊ฐ€ ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์— ๋Œ€ํ•ด์„  ์•„์ง ๋ช…ํ™•ํžˆ ๋ฐํ˜€์ง„ ๋ฐ”๊ฐ€ ์—†๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ์†Œ์•„ ์ฒญ์†Œ๋…„๊ธฐ์— 1ํ˜• ๋‹น๋‡จ๋กœ ์ง„๋‹จ ๋œ ํ™˜์ž๋“ค์„ ๊ฒฝ๊ณผ๊ด€์ฐฐ ํ•˜์—ฌ, non-dipper์™€ ๊ฐ™์€ ์ผ์ค‘ํ˜ˆ์••๋ณ€๋™์ด ๋ฏธ์„ธํ˜ˆ๊ด€ ํ•ฉ๋ณ‘์ฆ์˜ ๋ฐœ์ƒ์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์„ ํ‰๊ฐ€ํ•˜๊ณ ์ž ํ•œ๋‹ค. 2009๋…„ 1์›”๋ถ€ํ„ฐ 2010๋…„ 2์›” ๊นŒ์ง€ ์„œ์šธ๋Œ€ํ•™๊ต ์–ด๋ฆฐ์ด ๋ณ‘์›์—์„œ ์†Œ์•„์ฒญ์†Œ๋…„๊ธฐ์— 24์‹œ๊ฐ„ ํ™œ๋™ ํ˜ˆ์••์„ ์ธก์ •ํ•œ 81 ๋ช…์˜ 1ํ˜• ๋‹น๋‡จ ํ™˜์ž (๋‚จ์ž 33๋ช…, ์—ฌ์ž 48๋ช…)์˜ ์˜๋ฌด๊ธฐ๋ก์„ ํ›„ํ–ฅ์ ์œผ๋กœ ๋ถ„์„ํ•˜์˜€๋‹ค. non-dipper์™€ ๊ฐ™์€ ์ผ์ค‘ ํ˜ˆ์•• ๋ณ€๋™์ด 8๋…„ ์ถ”์ ๊ด€์ฐฐ ๊ธฐ๊ฐ„ ๋™์•ˆ ๋‹น๋‡จ๋ณ‘์„ฑ ๋ฏธ์„ธํ˜ˆ๊ด€ํ•ฉ๋ณ‘์ฆ์˜ ๋ฐœ์ƒ์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์„ ํ™•์ธํ•˜๊ธฐ ์œ„ํ•ด ํ˜ˆ๋‹น ์กฐ์ ˆ๊ณผ ์œ ๋ณ‘๊ธฐ๊ฐ„์„ ๋ณด์ • ํ•˜์—ฌ ํ‰๊ฐ€ํ•˜์˜€๋‹ค. ์—ฐ๊ตฌ์— ์ฐธ์—ฌํ•œ ํ™˜์ž๋“ค์˜ ํ‰๊ท  1ํ˜• ๋‹น๋‡จ ์ง„๋‹จ ๋‚˜์ด๋Š” 8.0 ยฑ 3.9 ์„ธ, 24์‹œ๊ฐ„ ํ™œ๋™ ํ˜ˆ์•• ์ธก์ •๋‹น์‹œ ๋‚˜์ด๋Š” 15.6 ยฑ 2.4 ์„ธ์˜€๋‹ค. ์ด๋“ค ์ค‘ ๊ณ ํ˜ˆ์•• (๋‚ฎ, ๋ฐค, 24์‹œ๊ฐ„ ํ‰๊ท )์€ 42๋ช… (51.9%) ์˜€๋‹ค. ๊ทธ๋ฆฌ๊ณ  ์ด๋“ค์˜ 24์‹œ๊ฐ„ ํ™œ๋™ํ˜ˆ์••๊ฒฐ๊ณผ๋กœ 3 ๊ทธ๋ฃน; dipper (n=30, 37.0%), ์ •์ƒํ˜ˆ์••๊ณผ non-dipper (n=18, 22.2%), ๊ณ ํ˜ˆ์••๊ณผ non-dipper (n=33, 40.7%) ์œผ๋กœ ๋‚˜๋ˆ„์—ˆ๋‹ค. 24์‹œ๊ฐ„ ํ™œ๋™ ํ˜ˆ์•• ์ธก์ • ํ›„ 8๋…„ ์ถ”์ ๊ด€์ฐฐ ๊ธฐ๊ฐ„ ๋™์•ˆ, ๋ฏธ์„ธํ˜ˆ๊ด€ ํ•ฉ๋ณ‘์ฆ์€ 8๋ช… (๋‹น๋‡จ๋ณ‘์„ฑ ๋ง๋ง‰๋ณ‘์ฆ 6๋ช…, ๋ฏธ์„ธ์•Œ๋ถ€๋ฏผ๋‡จ 3๋ช…, ๋ชจ๋‘ 1๋ช…) ์—์„œ ๋ฐœ์ƒํ•˜์˜€๊ณ , ๊ทธ ์ค‘ 7๋ช…์€ non-dipper์˜€๋‹ค. ๋‹น๋‡จ๋ณ‘์„ฑ ๋ง๋ง‰๋ณ‘์ฆ์ด ๋ฐœ์ƒํ•œ ํ™˜์ž๋“ค์˜ ๋ฐค์‹œ๊ฐ„ ์ด์™„๊ธฐ ํ˜ˆ์•• (1.29 ยฑ 1.06 SDS vs. 1.85 ยฑ 0.46 SDS)๊ณผ ๋ฐค์‹œ๊ฐ„ ํ‰๊ท  ๋™๋งฅ์•• (1.28 ยฑ 1.26 SDS vs. 1.98 ยฑ 0.57 SDS), ์ง„๋‹จ ์‹œ๋ถ€ํ„ฐ ๋ง๋ง‰๋ณ‘์ฆ์ด ๋ฐœ์ƒํ•˜๊ฑฐ๋‚˜ ๋งˆ์ง€๋ง‰ ์ถ”์ ๊ด€์ฐฐ ๊ธฐ๊ฐ„๊นŒ์ง€์˜ ๋‹นํ™”ํ˜ˆ์ƒ‰์†Œ ํ‰๊ท  (8.5 ยฑ 1.0 % vs. 10.1 ยฑ 0.7 %)์ด ๋ง๋ง‰๋ณ‘์ฆ์ด ๋ฐœ์ƒํ•˜์ง€ ์•Š์€ ํ™˜์ž๋“ค์— ๋น„ํ•ด ์œ ์˜ ํ•˜๊ฒŒ (p<0.05 for all) ๋†’์•˜๋‹ค. ๋‚ฎ ๋˜๋Š” ๋ฐค์‹œ๊ฐ„ ํ˜ˆ์••๊ณผ dipper์˜ ์œ ๋ฌด๋Š” ๋ฏธ์„ธํ˜ˆ๊ด€ํ•ฉ๋ณ‘์ฆ๊ณผ ๊ด€๋ จ์ด ์—†์—ˆ์œผ๋‚˜, ์ง„๋‹จ ์‹œ ๋‚˜์ด๊ฐ€ ๋งŽ์„์ˆ˜๋ก, ๋‹นํ™”ํ˜ˆ์ƒ‰์†Œ๊ฐ€ ๋†’์„์ˆ˜๋ก ๋‹น๋‡จ๋ณ‘์„ฑ ๋ฏธ์„ธํ˜ˆ๊ด€ํ•ฉ๋ณ‘์ฆ์ด ์ž˜ ๋ฐœ์ƒ ํ•˜์˜€์œผ๋ฉฐ, ์ง„๋‹จ ์‹œ ์‚ฌ์ถ˜๊ธฐ ์ธ ๊ฒฝ์šฐ์—๋Š” ๋ง๋ง‰๋ณ‘์ฆ์˜ ๋ฐœ์ƒ ์œ„ํ—˜์ด ํ†ต๊ณ„์ ์œผ๋กœ ์œ ์˜ํ•˜๊ฒŒ ๋†’์•˜๋‹ค (p-value < 0.05). ABPM ๊ฒฐ๊ณผ๋กœ ๋ถ„๋ฅ˜ํ•œ ์„ธ ๊ทธ๋ฃน์„ ๋น„๊ต ํ–ˆ์„ ๋•Œ, dipper, ์ •์ƒํ˜ˆ์•• non-dipper, ๊ณ ํ˜ˆ์•• non-dipper ์ˆœ์œผ๋กœ ๊ฐˆ์ˆ˜๋ก ๋‹น๋‡จ๋ณ‘์„ฑ ๋ง๋ง‰๋ณ‘์ฆ์ด ๋ฐœ์ƒ ๋น„์œจ์ด ์ฆ๊ฐ€ (0%, 16.7%, 83.3%, p=0.021) ํ–ˆ๋‹ค. ํ•˜์ง€๋งŒ, ๋ฏธ์„ธํ˜ˆ๊ด€ํ•ฉ๋ณ‘์ฆ ๋ฐœ์ƒ ์˜ˆ์ธก ์ธ์ž๋กœ cox ํšŒ๊ท€ ๋ถ„์„์„ ์‹œํ–‰ ํ–ˆ์„ ์‹œ, non-dipper์˜ ์œ ๋ฌด๋Š” ํ†ต๊ณ„์ ์œผ๋กœ ์œ ์˜๋ฏธํ•œ ๊ฒฐ๊ณผ๋Š” ๋ณผ ์ˆ˜ ์—†์—ˆ๋‹ค. ์ด ์—ฐ๊ตฌ๋ฅผ ํ†ตํ•˜์—ฌ ์†Œ์•„์ฒญ์†Œ๋…„๊ธฐ์— ์ง„๋‹จ๋œ 1ํ˜• ๋‹น๋‡จ ํ™˜์ž์—์„œ 24์‹œ๊ฐ„ ํ˜ˆ์•• ๋ณ€๋™ ๋ณด๋‹ค ํ˜ˆ๋‹น ์กฐ์ ˆ์ด ๋‹น๋‡จ๋ณ‘์„ฑ ๋ฏธ์„ธํ˜ˆ๊ด€ํ•ฉ๋ณ‘์ฆ ๋ฐœ์ƒ์— ์ฃผ๋กœ ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๊ฒƒ์„ ์•Œ ์ˆ˜ ์žˆ์—ˆ๋‹ค. ํ•˜์ง€๋งŒ, ํ˜ˆ์••๊ณผ ๋ฏธ์„ธํ˜ˆ๊ด€ํ•ฉ๋ณ‘์ฆ์ด ๊ด€๊ณ„๊ฐ€ ์—†๋‹ค๊ณ  ํ•  ์ˆ˜๋Š” ์—†์œผ๋ฉฐ, ์ถ”๊ฐ€์ ์ธ ์—ฐ๊ตฌ๊ฐ€ ํ•„์š”ํ•˜๋‹ค.Abstract .....................................................................................................................I Contents.....................................................................................................................IV List of tables and figures ..................................................................................V List of abbreviation...............................................................................................VI Introduction.................................................................................................................1 Materials and Methods...........................................................................................2 Results..........................................................................................................................6 Discussion..................................................................................................................18 References ................................................................................................................22 Abstract in Korean.................................................................................................23Maste

    ๋žซ๋“œ ๋‡Œ ํ—ˆํ˜ˆ์„ฑ ๋ชจ๋ธ์—์„œ ํ”„๋กœํ…Œ์•„์ œ ๊ฒฐ์† ์กฐ์งํ”Œ๋ผ์Šค๋ฏธ๋…ธ๊ฒ ํ™œ์„ฑ์ธ์ž์™€ ํ”ผ๋ฃจ๋ธŒ์‚ฐ์˜ ์น˜๋ฃŒํšจ๊ณผ

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์ˆ˜์˜ํ•™๊ณผ, 2014. 8. ์กฐ๋ช…ํ–‰.์ˆ˜์„ธ๊ธฐ ๋™์•ˆ ํ—ˆํ˜ˆ๋กœ ์ธํ•ด ์•ผ๊ธฐ๋˜๋Š” ๋‡Œ์กธ์ค‘ ์น˜๋ฃŒ ์•ฝ๋ฌผ์— ๋Œ€ํ•ด ๋งŽ์€ ์—ฐ๊ตฌ๊ฐ€ ์ง„ํ–‰ ๋˜์—ˆ์œผ๋‚˜ ์•„์ง๊นŒ์ง€ ํ‘œ์ค€ ์น˜๋ฃŒ์ œ๋ฅผ ์ฐพ์ง€ ๋ชปํ•˜๊ณ  ์žˆ๋Š” ์‹ค์ •์ด๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ๋‡Œ์กธ์ค‘ ์น˜๋ฃŒ ๊ฐ€๋Šฅ์„ฑ ์•ฝ๋ฌผ์„ ์ฐพ์•„ ๋žซ๋“œ๋ฅผ ์ด์šฉํ•œ ๋‡Œํ—ˆํ˜ˆ ๋ชจ๋ธ์— ํˆฌ์—ฌ ํ›„ ์น˜๋ฃŒ ํšจ๊ณผ๋ฅผ ์ฆ๋ช…ํ•˜๋Š” ๋ฐ์— ๋ชฉ์ ์„ ๋‘๊ณ  ์‹คํ–‰ํ•˜์˜€๋‹ค. ์ฒซ๋ฒˆ์งธ ๋‡Œ์กธ์ค‘ ์น˜๋ฃŒ ๊ฐ€๋Šฅ ์•ฝ๋ฌผ๋กœ ์žฌ์กฐํ•ฉ ์กฐ์ง ํ”Œ๋ผ์Šค๋ฏธ๋…ธ๊ฒ ํ™œ์„ฑ์ œ(tPA)์™€ ํ”„๋กœํ…Œ์•„์ œ ๊ฒฐ์† ์กฐ์งํ”Œ๋ผ์Šค๋ฏธ๋…ธ๊ฒ ํ™œ์„ฑ์ธ์ž(S478-tPA)๋ฅผ ์„ ํƒํ•˜์—ฌ ํšจ์†Œ ๋น„์˜์กด์„ฑ์œผ๋กœ ๋‡Œ์‹ค์งˆ ๋ณดํ˜ธ ํšจ๊ณผ๋ฅผ ํ™•์ธํ•˜์˜€๋‹ค. ๋‡Œ์กฐ์ง ์„ธํฌ ๋ฐฐ์–‘ ์กฐ๊ฑด์—์„œ๋Š” tPA์™€ S478A-tPA๋Š” ์•„์—ฐ์— ์˜ํ•œ ์„ธํฌ๋…์„ฑ์— ๋Œ€ํ•ด์„œ๋Š” ๋‡Œ์„ธํฌ ๋ณดํ˜ธ ํšจ๊ณผ๊ฐ€ ์žˆ์—ˆ๋‹ค. ๋žซ๋“œ ์˜๊ตฌ์ ์ธ ๋‡Œํ—ˆํ˜ˆ ๋ชจ๋ธ์— ์ค‘๋‡Œ๋™๋งฅํ์‡„ 15๋ถ„ ํ›„ ํ”Œ๋ผ์Šค๋ฏผ์ด ์ ์€ ๋‡Œ์‹ค๋กœ tPA์™€ S478A-tPA๋ฅผ ํˆฌ์—ฌ์‹œ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด 65.70% ๋‡Œ๊ฒฝ์ƒ‰์ด ๊ฐ์†Œ ๋˜์—ˆ๋‹ค. ๋‡Œํ—ˆํ˜ˆ ์ผ์ฃผ์ผ ์ดํ›„์—๋„ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด ๋‡Œ๊ฒฝ์ƒ‰ ๊ฐ์†Œ ํšจ๊ณผ์™€ ์šด๋™๊ฒฐ์†์ด ๊ฐœ์„ ๋˜๋Š” ๋‡Œ์กธ์ค‘ ์น˜๋ฃŒ ํšจ๊ณผ๋Š” ์ง€์†๋˜์—ˆ๋‹ค. ๋‘๋ฒˆ์งธ๋กœ ํ”ผ๋ฃจ๋ธŒ์‚ฐ์„ ์„ ํƒํ•˜์—ฌ ๋‡Œ์กธ์ค‘ ์น˜๋ฃŒํšจ๊ณผ๋ฅผ ๊ด€์ฐฐํ•˜์˜€๋‹ค. ํ”ผ๋ฃจ๋ธŒ์‚ฐ์„ ๋žซ๋“œ์˜ ์ผ์‹œ์  (1์‹œ๊ฐ„) ๋˜๋Š” ์˜๊ตฌ์  ๋‡Œํ—ˆํ˜ˆ ๋ชจ๋ธ์— ๋ณต๊ฐ• ๋˜๋Š” ์ •๋งฅ์ฃผ์‚ฌ๋กœ 62.5-250 mg/kg ๋†๋„๋กœ ํˆฌ์—ฌ์‹œ ํˆฌ์—ฌ๋ฐฉ๋ฒ•๊ณผ ๋†๋„์— ์ƒ๊ด€์—†์ด ๋‡Œ๊ฒฝ์ƒ‰์ด ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด 50%์ด์ƒ ์ค„์–ด๋“œ๋Š” ๊ฒƒ์„ ํ™•์ธ ํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ์˜๊ตฌ์ ์ธ ๋‡Œํ—ˆํ˜ˆ ๋ชจ๋ธ์—์„œ๋Š” ํˆฌ์—ฌ 14์ผ ์ดํ›„์—๋„ ๋‡Œ๊ฒฝ์ƒ‰๊ณผ ์šด๋™๊ฒฐ์†์„ ๊ฐ์†Œ์‹œํ‚ค๋Š” ๋‡Œ์กธ์ค‘ ์น˜๋ฃŒํšจ๊ณผ๋ฅผ ๋ณด์˜€๋‹ค. ํฅ๋ฏธ๋กญ๊ฒŒ๋„ ๋†’์€ ๋†๋„์˜ ํ”ผ๋ฃจ๋ธŒ์‚ฐํˆฌ์—ฌ๋Š” ๋‡Œ๊ฒฝ์ƒ‰์„ ๊ฐ์†Œ์‹œํ‚ค์ง€๋Š” ์•Š์•˜๋‹ค. ์ด๋Š” ์ˆ˜์†Œ์ž๊ธฐ๊ณต๋ช…๋ถ„๊ด‘๋ถ„์„์„ ํ†ตํ•œ ์ –์‚ฐ ๋†๋„ ์ธก์ •์‹œ ์น˜๋ฃŒ๋†๋„์— ๋น„ํ•ด ๋†’์€ ๋†๋„๋ฅผ ๋ณด์—ฌ์ฃผ๋Š” ๊ฒƒ์œผ๋กœ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. S478A-tPA๋Š” ๋‡Œ์ถœํ˜ˆ๊ณผ ํฅ๋ถ„์„ธํฌ๋…์„ฑ์„ ์ฆ๊ฐ€์‹œํ‚ค๋Š”๋ฐ ๊ด€์—ฌํ•˜๋Š” ๋‹จ๋ฐฑ์งˆ ํšจ์†Œ๋ถ„ํ•ดํ™œ์„ฑ ๊ธฐ๋Šฅ์€ ์—†์œผ๋ฉด์„œ ๋‡Œ์กฐ์ง์‹ค์งˆ์— ์‹ ๊ฒฝ๋ณดํ˜ธํšจ๊ณผ์™€ ๋‡Œ๊ฒฝ์ƒ‰์น˜๋ฃŒ์— ํšจ๊ณผ์ ์ด๋ผ๊ณ  ํ•  ์ˆ˜ ์žˆ๋‹ค. ํ”ผ๋ฃจ๋ธŒ์‚ฐ๋‚˜ํŠธ๋ฅจ๋Š” ์ธ์ฒด ๋‚ด์ƒ์˜ ํ•ด๋‹น์ž‘์šฉ ๋Œ€์‚ฌ์‚ฐ๋ฌผ๋กœ์„œ ์•Œ๋ ค์ง„ ๋ถ€์ž‘์šฉ์ด ๊ฑฐ์˜ ์—†๋Š” ๋ฌดํ•ดํ•œ ๋‹น์ด๋ฉฐ ์ €๊ฐ€์˜ ์•ฝ๋ฌผ์ด๋‹ค. ๋ณธ ์‹คํ—˜์˜ ๊ฒฐ๊ณผ๋กœ ์ด ๋‘๊ฐ€์ง€ ์•ฝ๋ฌผ์€ ์ธ์ฒด ๋ถ€์ž‘์šฉ์ด ์—†๋Š” ๋‡Œ์กธ์ค‘ ์น˜๋ฃŒ ํ›„๋ณด ์•ฝ๋ฌผ๋กœ ์‚ฌ์šฉ๊ฐ€๋Šฅ์„ฑ์„ ์ œ์‹œํ•  ์ˆ˜ ์žˆ๋‹ค.Despite intensive investigation over the last couple of decades, there is no standard parenchymal neuroprotective treatment available for ischemic stroke. So, we find to possible agent for ischemic stroke treatment. The purpose of this study was to examine the therapeutic effects of candidate agents in rat brain ischemia model. At the first, we examined parenchymal effects of tPA and its non-protease mutant S478A-tPA in permanent focal cerebral ischemia in rats. Before doing in vivo experiments, effects of tPA and S478A-tPA on zinc or NMDA toxicity were first studied in cortical cultures. Like tPA, which has protease-independent cytoprotective effects, the non-protease mutant S478A-tPA blocked zinc toxicity in cortical cell cultures, but did not affect calcium-mediated NMDA toxicity. Then, effects of tPA and S478A-tPA on infarcts induced by permanent occlusion of middle cerebral artery (MCA) were investigated. tPA and S478A-tPA were administered into the cerebral ventricle 15 min or 1 h after MCA occlusion. Both tPA and its non-protease mutant S478A-tPA, when given 15 min after ischemia, substantially reduced infarcts and ameliorated motor deficits in the MCA occlusion model of focal cerebral ischemia. However, when administered 1 h after MCA occlusion, neither showed protective effects. The protective effects of tPA or S478A-tPA remained unchanged at 7 days after MCA occlusion. At the second, we examined the therapeutic effects of pyruvate in focal cerebral ischemia in rats. Pyruvate markedly reduces neuronal death following transient global ischemia. In the present study, we investigated the possible neuroprotective effect of pyruvate in focal ischemia. Pyruvate (62.5โ€“250 mg/kg) treatment, regardless of whether given intraperitoneally (ip) or intravenously (iv), decreased infarct volume by more than 50% in both transient (1 h) and permanent occlusion models. The infarct reducing effects of pyruvate were maintained for 14 days after MCAO. Interestingly, higher doses failed to reduce the infarct size. Pyruvate administration also reduced motor deficits. Magnetic resonance (MR) spectroscopy revealed that protective doses of pyruvate, but not the non-protective doses, were associated with a reduction in the level of lactate compared with saline controls. Diffusion-weighted MR images further confirmed infarct reduction in pyruvate-treated rats. Since S478A-tPA lacks protease activity, which has been implicated in causing cerebral hemorrhage or aggravating excitotoxicity, its parenchymal neuroprotective effect may be useful in treatment of ischemic stroke. In addition, pyruvate is an endogenous metabolite of glycolysis, and hence is unlikely to have serious side effects. The combined use of a neuroprotective agent would enhance neuron survival and thereby extend the window of opportunity for thrombolytic treatment to potentially benefit more patients.Abstract List of Tables List of Figures Chapter 1. General Introduction 1. The occurrence of stroke 2. Medical uses of tissue plasminogen activator 3. Properties of pyruvate Chapter 2. Infarct reduction in rats following intraventricular administration of either tissue plasminogen activator (tPA) or its non-protease mutant S478A-tPA 1. Abstract 2. Introduction 3. Materials and Methods 4. Results 5. Discussion Chapter 3. Systemic pyruvate administration markedly reduces infarcts and moter deficits in rat models of transient and permanent focal cerebral ischemia 1. Abstract 2. Introduction 3. Materials and Methods 4. Results 5. Discussion Chapter 4. General Conclusion Chapter 5. References Chapter 6. Abstract in KoreanDocto

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ํ–‰์ •๋Œ€ํ•™์› : ํ–‰์ •ํ•™๊ณผ ํ–‰์ •ํ•™์ „๊ณต, 2016. 8. ๊ธˆํ˜„์„ญ.์—ฌ์„ฑ ๊ณ ์šฉ์€ ๊ตญ๊ฐ€ ์ž ์žฌ ์„ฑ์žฅ๋ ฅ์„ ๋‹ด๋ณดํ•˜๋Š” ๊ฐ€์žฅ ์ค‘์š”ํ•œ ๋ฐฉ์•ˆ์œผ๋กœ ์ธ์‹๋˜๊ณ  ์žˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ์šฐ๋ฆฌ๋‚˜๋ผ ์—ฌ์„ฑ ๊ณ ์šฉ๋ฅ ์€ 2013๋…„ 49.5%๋กœ ์„ธ๊ณ„์ตœํ•˜์œ„ ์ˆ˜์ค€์ด๋ฉฐ ์ด๋Š” 2003๋…„ 49.0%๊ณผ ๋น„๊ตํ•ด ๊ฑฐ์˜ ๋ณ€ํ™”๊ฐ€ ์—†๋Š” ์ƒํ™ฉ์ด๋‹ค. ๋Œ€ํ†ต๋ น์˜ ํ•ต์‹ฌ๊ณต์•ฝ์— ์—ฌ์„ฑ ๊ณ ์šฉ๋ฅ  ์ œ๊ณ ๋ฅผ ์œ„ํ•œ ์ผ ๊ฐ€์ • ์–‘๋ฆฝ ์ •์ฑ…์ด ํฌํ•จ๋˜๊ณ , ์ตœ๊ทผ 5๋…„๊ฐ„ ๋ณด์œก์˜ˆ์‚ฐ์ด 2๋ฐฐ๊ฐ€ ๋„˜๊ฒŒ ์ฆ๊ฐ€ํ•˜๋Š” ๋“ฑ ๋ณด์œก์ •์ฑ…์ด ์ง€์†์ ์œผ๋กœ ๊ฐ•ํ™”๋˜๊ณ  ์žˆ์Œ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ  ์ผํ•˜๋Š” ์—ฌ์„ฑ๋“ค์€ ์—ฌ์ „ํžˆ ์ž๋…€ ์–‘์œก๋ฌธ์ œ๋ฅผ ์ผ๊ณผ ๊ฐ€์ •์˜ ์–‘๋ฆฝ์— ์žˆ์–ด์„œ ๊ฐ€์žฅ ํฐ ์žฅ์• ์š”์ธ์œผ๋กœ ์ง€์ ํ•˜๊ณ  ์žˆ๋‹ค. ์œก์•„๋ฅผ ๋Œ€์ฒดํ•  ์ˆ˜ ์žˆ๋Š” ์ˆ˜๋‹จ์€ ์—ฌ์„ฑ ๊ณ ์šฉ์— ์žˆ์–ด ํ•„์ˆ˜์ ์ธ ์ „์ œ์กฐ๊ฑด์ด๋ฉฐ, ์—ฌ์„ฑ์˜ ์ทจ์—… ์ง€์† ์—ฌ๋ถ€๋ฅผ ๊ฒฐ์ •ํ•˜๋Š”๋ฐ ๊ฐ€์žฅ ์ง์ ‘์ ์ธ ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ์š”์ธ์ด๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ์ด์ œ๊นŒ์ง€ ์ผํ•˜๋Š” ์—ฌ์„ฑ์˜ ๊ตฌ์ฒด์ ์ธ ์œก์•„ ๋Œ€์ฒด ๋ฐฉ์‹๊ณผ ์ทจ์—… ์—ฐ์†์„ฑ์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๊ฐ€ ์ถฉ๋ถ„ํžˆ ์ง„ํ–‰๋˜์ง€ ๋ชปํ•œ ์ธก๋ฉด์ด ์žˆ๋‹ค. ์„ ํ–‰์—ฐ๊ตฌ๋“ค์€ ์–‘์œก๊ณผ ๊ด€๋ จ๋œ ์š”์ธ์œผ๋กœ ์ž๋…€์ˆ˜, ๋ณด์œก์กฐ๋ ฅ์ž ์œ ๋ฌด ๋“ฑ์— ํ•œ์ •ํ•˜์—ฌ ๋ถ„์„์„ ํ•˜์˜€๊ธฐ ๋•Œ๋ฌธ์ด๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ์—ฐ๊ตฌ๋Š” ์ผํ•˜๋Š” ์—ฌ์„ฑ์˜ ์ž๋…€ ์–‘์œกํ˜•ํƒœ๊ฐ€ ์ทจ์—…์—ฐ์†์„ฑ์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์„ ๋ถ„์„ํ•˜์˜€๋‹ค. ์–‘์œก๋Œ€์ฒด ํ˜•ํƒœ๋Š” ์กฐ๋ถ€๋ชจ ๋“ฑ์ด ์†์ž๋…€๋ฅผ ์–‘์œกํ•˜๋Š” ๊ฐœ๋ณ„๋ณด์œก๊ณผ ์–ด๋ฆฐ์ด์ง‘ยท์œ ์น˜์› ๋“ฑ์„ ์ด์šฉํ•˜๋Š” ์‹œ์„ค๋ณด์œก์œผ๋กœ ๋‚˜๋ˆ„์–ด, ๊ฐ๊ฐ์˜ ์ด์šฉ์—ฌ๋ถ€์™€ ์ด์šฉ์‹œ๊ฐ„, ์ด ์œก์•„๋Œ€์ฒด์‹œ๊ฐ„์—์„œ ๊ฐœ๋ณ„๋ณด์œก์ด ์ฐจ์ง€ํ•˜๋Š” ๋น„์ค‘์„ ์„ค๋ช…๋ณ€์ˆ˜๋กœ ํ•˜์˜€๋‹ค. ์ข…์†๋ณ€์ˆ˜์ธ ์ทจ์—…์—ฐ์†์„ฑ์€ ์ง€๋‚œ ์กฐ์‚ฌ๋‹น์‹œ ์ผ์ž๋ฆฌ์—์„œ ์ผ์„ ์ง€์†ํ•˜๋Š” ์‚ฌ๋žŒยท์ƒˆ๋กœ์šด ์ผ์ž๋ฆฌ๋กœ ์ด์งํ•œ ์‚ฌ๋žŒยท์ผ์ž๋ฆฌ๋ฅผ ๊ทธ๋งŒ๋‘” ์‚ฌ๋žŒ์œผ๋กœ ๋ถ„๋ฅ˜ํ•˜์˜€๋‹ค. ๊ฐ ๋ณ€์ˆ˜์™€ ์ทจ์—…์—ฐ์†์„ฑ๊ณผ์˜ ๊ด€๊ณ„๋ฅผ ์•Œ์•„๋ณด๊ธฐ ์œ„ํ•˜์—ฌ ์—ฌ์„ฑ๊ฐ€์กฑํŒจ๋„ 3์ฐจ์™€ 4์ฐจ ์ž๋ฃŒ๋ฅผ ์ด์šฉํ•˜์—ฌ ๋กœ์ง“ ๋ถ„์„์„ ์‹ค์‹œํ•˜์˜€๊ณ , ์—ญ(reverse)์ธ๊ณผ๊ด€๊ณ„ ๊ฐ€๋Šฅ์„ฑ์„ ๋ฐฐ์ œํ•˜๊ธฐ ์œ„ํ•ด ๋…๋ฆฝ๋ณ€์ˆ˜์™€ ์ข…์†๋ณ€์ˆ˜๊ฐ„ ์‹œ์ฐจ๋ฅผ ๋‘์–ด ๋ถ„์„ํ•˜์˜€๋‹ค. ๋ถ„์„ ๊ฒฐ๊ณผ, ๊ฐœ๋ณ„๋ณด์œก ์œ ๋ฌด, ์‹œ์„ค๋ณด์œก ์œ ๋ฌด๋Š” ์ทจ์—…์—ฐ์†์„ฑ์— ์œ ์˜๋ฏธํ•œ ์˜ํ–ฅ์„ ๋ฏธ์น˜์ง€ ์•Š์•˜์ง€๋งŒ, ๊ฐœ๋ณ„๋ณด์œก ์‹œ๊ฐ„๊ณผ ์ด ์œก์•„๋Œ€์ฒด์‹œ๊ฐ„ ์ค‘ ๊ฐœ๋ณ„๋ณด์œก์‹œ๊ฐ„์˜ ๋น„์ค‘์ด ์ทจ์—…์—ฐ์†์„ฑ์— ์œ ์˜๋ฏธํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ๊ฐœ๋ณ„๋ณด์œก๊ณผ ์‹œ์„ค๋ณด์œก์˜ ์˜ํ–ฅ์„ ๋™์‹œ์— ๋ถ„์„ํ•˜์—ฌ, ์‹œ์„ค๋ณด์œก ์ด์šฉ ์—ฌ๋ถ€๊ฐ€ ํ†ต์ œ๋œ ์ƒํ™ฉ์—์„œ๋„ ๊ฐœ๋ณ„๋ณด์œก ์‹œ๊ฐ„์ด ์ทจ์—…์—ฐ์†์„ฑ์— ์œ ์˜๋ฏธํ•œ ์˜ํ–ฅ์„ ๋ฏธ์นœ๋‹ค๊ณ  ํ•ด์„ํ•  ์ˆ˜ ์žˆ๋‹ค. ๋˜ํ•œ, ์‹œ๊ฐ„์„ ๋ณ€์ˆ˜๋กœ ๋„์ž…ํ•˜์—ฌ ๋Œ๋ด„์˜ ๊ฐ•๋„์— ๋”ฐ๋ฅธ ์˜ํ–ฅ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ์—ฐ๊ตฌ ๊ฒฐ๊ณผ๋Š” ๊ฐœ๋ณ„๋ณด์œก์— ๋Œ€ํ•œ ์ง€์›์ด ์ผ ๊ฐ€์ • ์–‘๋ฆฝ ์ •์ฑ…์— ํฌํ•จ๋˜์–ด์•ผ ํ•œ๋‹ค๋Š” ์‹œ์‚ฌ์ ์„ ์ค„ ์ˆ˜ ์žˆ๋‹ค. ํ•˜์ง€๋งŒ ๊ถ๊ทน์ ์œผ๋กœ๋Š” ๋ถ€๋ชจ๊ฐ€ ๊ฐœ๋ณ„๋ณด์œก์˜ ๋„์›€ ์—†์ด๋„ ์ทจ์—…์„ ์œ ์ง€ํ•  ์ˆ˜ ์žˆ๋„๋ก ์žฅ์‹œ๊ฐ„ ๊ทผ๋กœ ๊ด€ํ–‰ ๊ฐœ์„ ์ด ํ•„์š”ํ•  ๊ฒƒ์ด๋‹ค. ์ด๋Š” ๊ฐœ๋ณ„๋ณด์œก์˜ ํ•„์š”์„ฑ ์ž์ฒด๊ฐ€ ๊ฐœ๋ณ„๋ณด์œก์„ ์ด์šฉํ•˜๊ธฐ ์–ด๋ ค์šด ์‚ฌ๋žŒ์—๊ฒŒ๋Š” ๋…ธ๋™์‹œ์žฅ์—์„œ์˜ ์ฐจ๋ณ„์  ์ถœ๋ฐœ์ ์ด ๋  ์ˆ˜ ์žˆ๊ธฐ ๋•Œ๋ฌธ์ด๋‹ค.์ œ 1์žฅ ์„œ ๋ก  : ์—ฐ๊ตฌ๋ฐฐ๊ฒฝ ๋ฐ ํ•„์š”์„ฑ 1 ์ œ 2์žฅ ์„ ํ–‰์—ฐ๊ตฌ 5 ์ œ 1์ ˆ ๊ธฐํ˜ผ์—ฌ์„ฑ์˜ ๊ณ ์šฉ์— ๊ด€ํ•œ ์ด๋ก ์  ๋…ผ์˜ 5 ์ œ 2์ ˆ ์ผํ•˜๋Š” ์—ฌ์„ฑ์˜ ์ทจ์—…์—ฐ์†์„ฑ์— ๊ด€ํ•œ ์„ ํ–‰์—ฐ๊ตฌ 6 ์ œ 3์ ˆ ์ผํ•˜๋Š” ์—ฌ์„ฑ์˜ ์œก์•„ํ˜•ํƒœ์— ๊ด€ํ•œ ์„ ํ–‰์—ฐ๊ตฌ 10 ์ œ 4์ ˆ ์ผํ•˜๋Š” ์—ฌ์„ฑ์˜ ์œก์•„ํ˜•ํƒœ์™€ ์ทจ์—…์—ฐ์†์„ฑ์˜๊ด€๊ณ„์— ๊ด€ํ•œ ์„ ํ–‰์—ฐ๊ตฌ 14 ์ œ 3์žฅ ์—ฐ๊ตฌ ์„ค๊ณ„ 20 ์ œ 1์ ˆ ์—ฐ๊ตฌ ๊ฐ€์„ค ๋„์ถœ 20 ์ œ 2์ ˆ ์ž๋ฃŒ ๋ฐ ๋ถ„์„๋Œ€์ƒ 24 ์ œ 3์ ˆ ๋ณ€์ˆ˜ 25 1. ์ข…์†๋ณ€์ˆ˜ 25 2. ๋…๋ฆฝ๋ณ€์ˆ˜ 28 3. ํ†ต์ œ๋ณ€์ˆ˜ 31 ์ œ 4์ ˆ ๋ถ„์„ ๋ฐฉ๋ฒ• 31 ์ œ 4์žฅ ๋ถ„์„ ๊ฒฐ๊ณผ 33 ์ œ 1์ ˆ ๊ธฐ์ˆ ํ†ต๊ณ„๋ถ„์„ 33 1. ์‘๋‹ต์ž ํŠน์„ฑ 33 2. ์œก์•„ํ˜•ํƒœ 36 3. ์ผํ•˜๋Š” ์—ฌ์„ฑ์˜ ์ทจ์—… ์—ฐ์†์„ฑ 41 ์ œ 2์ ˆ ๋กœ์ง€์Šคํ‹ฑ ํšŒ๊ท€๋ถ„์„ 43 1. ๋ชจ๋ธ1์˜ ๋ถ„์„๊ฒฐ๊ณผ 43 2. ๋ชจ๋ธ2์˜ ๋ถ„์„๊ฒฐ๊ณผ 47 3. ๋ชจ๋ธ3์˜ ๋ถ„์„๊ฒฐ๊ณผ 50 4. ๋ถ„์„๊ฒฐ๊ณผ ์š”์•ฝ 56 ์ œ 5์žฅ ๊ฒฐ๋ก  ๋ฐ ์ •์ฑ…์  ํ•จ์˜ 57 ์ œ 1์ ˆ ์—ฐ๊ตฌ ๊ฒฐ๊ณผ ์š”์•ฝ 57 ์ œ 2์ ˆ ์ •์ฑ…์  ์‹œ์‚ฌ์  59 ์ œ 3์ ˆ ์—ฐ๊ตฌ์˜ ์˜์˜ ๋ฐ ํ•œ๊ณ„ 62 ์ฐธ๊ณ  ๋ฌธํ—Œ 65 ABSTRACT 71Maste

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    A Study on China Urban Subsistence Allowance Childrens Welfare Needs and Chinas Assistance System in Dalian -Focusing on Community Subsistence Allowance Staffs Perspectiveโ€“

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์‚ฌํšŒ๋ณต์ง€ํ•™๊ณผ, 2015. 8. ๋ฐ•์ •๋ฏผ.๋ณธ ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์€ ์ง€์—ญ์‚ฌํšŒ์œ„์›ํšŒ์˜ ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์š”์›์ด ์ธ์‹ํ•˜๋Š” ์ค‘๊ตญ ๋‹ค๋ก„์‹œ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์˜ ๋ณต์ง€์š•๊ตฌ, ๊ด€๋ จ ๋ณต์ง€ ์ •์ฑ…๊ณผ ์„œ๋น„์Šค์˜ ํ˜„ํ™ฉ, ๊ทธ๋ฆฌ๊ณ  ๋ณต์ง€์š•๊ตฌ์™€ ์ •์ฑ… ๋ฐ ์„œ๋น„์Šค์˜ ๋ถ€ํ•ฉ ์ˆ˜์ค€์„ ํŒŒ์•…ํ•˜๋Š” ๊ฒƒ์ด๋‹ค. ์ด๋ฅผ ์œ„ํ•ด 2015๋…„ 1~2์›” ๋‘ ๋‹ฌ ๋™์•ˆ ์ค‘๊ตญ ๋‹ค๋ก„์‹œ์—์„œ ์ง€์—ญ์‚ฌํšŒ์œ„์›ํšŒ์— ์†ํ•œ 43๋ช…์˜ ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์š”์›์— ๋Œ€ํ•œ ์ธํ„ฐ๋ทฐ๋ฅผ ์‹ค์‹œํ•˜์˜€๋‹ค. ์—ฐ๊ตฌ๊ฒฐ๊ณผ๋ฅผ ๋ฐ”ํƒ•์œผ๋กœ ๋‹ค๋ก„์‹œ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์„ ์œ„ํ•œ ์ง€์› ์ฒด๊ณ„์™€ ์•„๋™์˜ ๋ณต์ง€์š•๊ตฌ์™€์˜ ์ผ์น˜์—ฌ๋ถ€๋ฅผ ๋ถ„์„ํ•˜๊ณ  ๋‚˜์•„๊ฐ€ ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์„ ์œ„ํ•œ ๋ณต์ง€ ์ง€์› ์ฒด๊ณ„, ํŠนํžˆ ์•„๋™์˜ ๋ฐœ๋‹ฌ ๋‹จ๊ณ„์— ๊ธฐ๋ฐ˜ํ•œ ์š•๊ตฌ์— ๋งž๋Š” ์ง€์›์ฒด๊ณ„ ์ˆ˜๋ฆฝ์˜ ๋ฐฉํ–ฅ์„ ์ œ์‹œํ•˜์˜€๋‹ค. ์ฃผ์š” ์—ฐ๊ตฌ๊ฒฐ๊ณผ๋Š” ๋‹ค์Œ๊ณผ ๊ฐ™๋‹ค. ์ฒซ์งธ, ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์š”์›์ด ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์—๊ฒŒ ๊ฐ€์žฅ ํ•„์š”ํ•˜๋‹ค๊ณ  ์ƒ๊ฐํ•˜๋Š” ๋‹ค์„ฏ ๊ฐ€์ง€ ๋ณต์ง€์š•๊ตฌ๋Š” ์•„๋™์˜ ์ค‘๋Œ€์งˆํ™˜ ์น˜๋ฃŒ๋น„ ์ง€์›(์ฒ˜๋ฐฉ์•ฝ๋น„ ํฌํ•จ), ๊ณ ๋“ฑํ•™๊ต ํ•™๋น„ ์ง€์›, ๊ณ ๋“ฑํ•™๊ต ๊ต๊ตฌ/๊ต์žฌ ๊ตฌ์ž… ๋น„์šฉ ์ง€์›, ์ดˆ?์ค‘?๊ณ  ํ•™๊ต ๊ธ‰์‹๋น„ ์ง€์›, ์•„๋™์˜ ์™ธ๋ž˜ ๋ฐ ์ž…์› ์น˜๋ฃŒ๋น„ ์ง€์›(์ฒ˜๋ฐฉ์•ฝ๋น„ ํฌํ•จ)์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ๋‘˜์งธ, ๋‹ค๋ก„์‹œ์˜ ํ˜„ํ–‰ ์ฃผ์š” ๋ณต์ง€ ์ •์ฑ…๊ณผ ์„œ๋น„์Šค๋Š” ์ฃผ๋กœ ๋„์‹œ ์ฃผ๋ฏผ ์ค‘๋Œ€์งˆํ™˜ ์˜๋ฃŒ๋ณดํ—˜, ์ž„์‹œ๊ตฌํ˜ธ(่‡จๆ™‚ๆ•‘ๅŠฉ)์ œ๋„, ์ž์„ ์ดํšŒ(ๆ…ˆๅ–„็ธฝๆœƒ)์˜ ์ง€์› ํ”„๋กœ๊ทธ๋žจ, ๊ณ ๋“ฑํ•™๊ต ๊ตญ๊ฐ€ ๋ณด์กฐ๊ธˆ ์ œ๋„[้ซ˜ไธญๅœ‹ๅฎถๅŠฉๅญธ้‡‘ๅˆถๅบฆ], ์ง์—…๊ณ ๋“ฑํ•™๊ต (์ง์—…์ค‘๋“ฑํ•™๊ต)์˜ ๊ต์œก๋น„ ์ง€์›, ์ž„์‹œ๋ฌผ์ž๊ตฌ์ œ(่‡จๆ™‚็‰ฉ่ณ‡ๆ•‘ๆฟŸ) ๋“ฑ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ์…‹์งธ, ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์š”์›์ด ์ธ์‹ํ•˜๋Š” ๋‹ค๋ก„์‹œ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์˜ ๋ณต์ง€์š•๊ตฌ์™€ ํ˜„ํ–‰ ๋ณต์ง€ ์ •์ฑ… ๋ฐ ์„œ๋น„์Šค๊ฐ€ ์–ผ๋งˆ๋‚˜ ๋ถ€ํ•ฉํ•˜๋Š”์ง€ ์กฐ์‚ฌํ•œ ๊ฒฐ๊ณผ, ๋งŽ์€ ์š”์›๋“ค์ด ํ˜„ํ–‰ ๋ณต์ง€ ์ •์ฑ… ๋ฐ ์„œ๋น„์Šค์— ๋Œ€ํ•ด ์ถฉ์กฑํ•จ ๋ฐ ๋งค์šฐ ์ถฉ์กฑํ•จ(39.5%)์˜ ๊ธ์ •์ ์ธ ์ธ์‹์„ ๊ฐ€์ง€๊ณ  ์žˆ์—ˆ๊ณ  27.9%์˜ ์š”์›๋“ค์€ ๋ณดํ†ต์ด๋‹ค์˜ ์ธ์‹์„ ๊ฐ€์ง€๊ณ  ์žˆ์—ˆ๋‹ค. ๋ฐ˜๋ฉด ๋ฏผ๊ฐ„ ์ง€์›์— ๋Œ€ํ•ด์„œ๋Š” ์ถฉ์กฑํ•จ ๋ฐ ๋งค์šฐ ์ถฉ์กฑํ•จ์˜ ๊ธ์ •์ ์ธ ์ธ์‹์„ ๊ฐ€์ง€๊ณ  ์žˆ๋Š” ์š”์›๋“ค์ด 11.0%์— ๋ถˆ๊ณผํ–ˆ๊ณ , 34.9%์˜ ์š”์›๋“ค์€ ๋ณดํ†ต์ด๋‹ค์˜ ์ธ์‹์„ ๊ฐ€์ง€๊ณ  ์žˆ์—ˆ๋‹ค. ์š”์›๋“ค์ด ์ธ์‹ํ•˜๋Š” ์•ž์œผ๋กœ ์‹คํ–‰์ด ํ•„์š”ํ•œ ๋ณต์ง€ ์ •์ฑ… ๋ฐ ์„œ๋น„์Šค๋Š” ์‚ฌํšŒ์„ฑ(ํ•™๊ต๋‚ด ์ผ๋ฐ˜ ํ™œ๋™), ๊ต์œก(์ดˆ?์ค‘?๊ณ  ๊ณ ๊ธ‰ ๋ฌธ๊ตฌ ์ง€์›), ๋Œ๋ด„(๋ฐฉ๊ณผํ›„ ๋ฐ ๋ฐฉํ•™์ค‘ ๋Œ๋ด„ ์„œ๋น„์Šค) ์„ธ ๊ฐ€์ง€ ์˜์—ญ์— ์ง‘์ค‘๋˜์—ˆ๊ณ , ํ˜„ํ–‰ ์ง€์› ์ˆ˜์ค€์ด ๋‚ฎ์•„ ํ™•๋Œ€ํ•  ํ•„์š”๊ฐ€ ์žˆ๋Š” ๋ถ„์•ผ๋Š” ๋ณด๊ฑด์˜๋ฃŒ(์•„๋™์˜ ์™ธ๋ž˜ ๋ฐ ์ž…์› ์น˜๋ฃŒ๋น„, ์•„๋™์˜ ์ค‘๋Œ€์งˆํ™˜ ์น˜๋ฃŒ๋น„) ์˜์—ญ์ด ๊ผฝํžˆ์—ˆ๋‹ค. ์—ฐ๊ตฌ ๊ฒฐ๊ณผ์˜ ์ •์ฑ…์ , ์‹ค์ฒœ์  ํ•จ์˜๋Š” ๋‹ค์Œ๊ณผ ๊ฐ™๋‹ค. ์ฒซ์งธ, ํ˜„ํ–‰ ์ง€์›์ธ ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์ œ๋„, ์˜๋ฌด๊ต์œก ์ œ๋„ ๊ทธ๋ฆฌ๊ณ  ๋„์‹œ ์ฃผ๋ฏผ ์ค‘๋Œ€์งˆํ™˜ ์˜๋ฃŒ๋ณดํ—˜ ์ œ๋„์˜ ์ง€์› ๊ฐ•๋„๊ฐ€ ๋ถ€์กฑํ•จ์œผ๋กœ ์•ž์œผ๋กœ ์ง€์›์˜ ๋ฒ”์œ„๊ฐ€ ํ™•๋Œ€๋  ํ•„์š”๊ฐ€ ์žˆ๋‹ค. ํŠนํžˆ ๋ณด๊ฑด์˜๋ฃŒ ๋ฐ ๊ต์œก ๋‘ ๊ฐ€์ง€ ๋ถ„์•ผ์— ๋Œ€ํ•œ ์ง€์› ์ˆ˜์ค€์ด ๋ถ€์กฑํ•˜๋‹ค. ๋ณด๊ฑด์˜๋ฃŒ์— ๊ด€ํ•œ ํ˜„ํ–‰ ๋ณต์ง€ ์ •์ฑ…์€ ์ง€์›ํ•˜๋Š” ์งˆํ™˜ ์ข…๋ฅ˜ ๋ฐ ์ง€์›๊ธˆ์˜ ๋ฒ”์œ„๋ฅผ ํ™•๋Œ€ํ•  ํ•„์š”๊ฐ€ ์žˆ์œผ๋ฉฐ, ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์ด ์ผ๋ฐ˜์งˆํ™˜๊ณผ ์ค‘๋Œ€์งˆํ™˜์— ๋Œ€ํ•œ ๋ณด์žฅ์„ ๋ฐ›์„ ์ˆ˜ ์žˆ๋„๋ก ์ง€์›๋ฒ”์œ„๋ฅผ ํ™•๋Œ€ํ•  ํ•„์š”๊ฐ€ ์žˆ๋‹ค. ๊ต์œก์˜ ๊ฒฝ์šฐ, ์˜๋ฌด๊ต์œก์„ ๋ฐ”ํƒ•์œผ๋กœ ๊ต์œก ๊ณผ์ • ์ „๋‹จ๊ณ„์— ๋Œ€ํ•œ ํ•™๊ต ๊ธ‰์‹๋น„ ์ง€์›, ๊ณ ๋“ฑํ•™๊ต ๋‹จ๊ณ„์˜ ๊ต๋ณต๋น„, ๊ต์žฌ๋น„ ๋“ฑ ๋น„์šฉ์— ๋Œ€ํ•œ ์ง€์›์œผ๋กœ ํ™•๋Œ€ํ•  ํ•„์š”๊ฐ€ ์žˆ๋‹ค. ๋‘˜์งธ, ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์— ๋Œ€ํ•œ ๊ฐ€์žฅ ์ค‘์š”ํ•œ ์ง€์› ์ œ๋„์ธ ์ค‘๊ตญ์˜ ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์ œ๋„๋Š” ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ๋‹จ์œ„๋กœ ์ƒ๊ณ„๋น„ ์ง€์›๋งŒ์ด ์ด๋ฃจ์–ด์ง€๊ณ  ์žˆ๋Š”๋ฐ, ์•„๋™์˜ ํŠน์„ฑ์— ๊ทผ๊ฑฐํ•œ ์ง€์›์ด ๋ถ€์กฑํ•˜๊ธฐ ๋•Œ๋ฌธ์— ์•ž์œผ๋กœ ์•„๋™์˜ ๋ฐœ๋‹ฌ ์š•๊ตฌ๋ฅผ ๊ณ ๋ คํ•œ ๋งž์ถคํ˜• ์ง€์› ์ฒด๊ณ„๋กœ ๋ฐœ์ „๋  ํ•„์š”๊ฐ€ ์žˆ๋‹ค. ์…‹์งธ, ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์˜ ์š•๊ตฌ ํŒŒ์•… ๋ฐ ๊ด€๋ จ ์„œ๋น„์Šค ์ œ๊ณต๊ณผ ๊ด€๋ จ๋œ ๊ทœ์ •์ด ์—†๊ธฐ ๋•Œ๋ฌธ์— ํ‘œ์ค€ํ™”๋œ ๊ธฐ์ค€๊ณผ ๊ทœ์ •์„ ๋งŒ๋“ค ํ•„์š”๊ฐ€ ์žˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ์ค‘๊ตญ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์˜ ๊ธฐ๋ณธ์š•๊ตฌ๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ์•„๋™๋ฐœ๋‹ฌ๋‹จ๊ณ„์— ๋”ฐ๋ผ ์–ด๋–ค ๋ณต์ง€์š•๊ตฌ๊ฐ€ ์žˆ๋Š”๊ฐ€์— ๊ด€ํ•œ ์ •๋ณด, ๋˜ํ•œ ์ƒ์กด์— ๊ด€ํ•œ ์ง€์›๋ณด๋‹ค ์•„๋™๋ฐœ๋‹ฌ๋‹จ๊ณ„์— ์ดˆ์ ์„ ๋‘” ์ง€์›๋Œ€์ฑ…์˜ ํ˜„ํ™ฉ๊ณผ ํ•„์š”์„ฑ์„ ์กฐ์‚ฌํ•œ ํƒ์ƒ‰์ ์ธ ์—ฐ๊ตฌ์ด๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ๊ฒฐ๊ณผ๋ฅผ ํ†ตํ•˜์—ฌ ๋‹ค๋ก„์‹œ์˜ ๋„์‹œ ๋นˆ๊ณค ์•„๋™๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ์ค‘๊ตญ ํƒ€ ๋„์‹œ์˜ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์„ ์œ„ํ•œ ๋ณต์ง€ ์ง€์› ์ฒด๊ณ„๋ฅผ ๋ณด์™„ํ•˜๋Š” ๋ฐ์— ์ฐธ๊ณ ํ•  ์ˆ˜ ์žˆ์„ ๊ฒƒ์œผ๋กœ ๊ธฐ๋Œ€๋œ๋‹ค. ์ฃผ์š”์–ด: ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์ œ๋„, ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์ˆ˜๊ธ‰ ๊ฐ€๊ตฌ ์•„๋™, ๋ณต์ง€์š•๊ตฌ, ์•„๋™์„ ์œ„ํ•œ ์ง€์› ์ฒด๊ณ„ ํ•™๋ฒˆ: 2012-23896This article focuses on the topics of urban subsistence allowance for childrens welfare needs in Dalian, China. The current assistance system for children and the matching degree of both in Dalian China will be looked at through the perspective of community subsistence allowance staff. The approach to solve this problem was conducted with interviews and surveyed a total of 43 community subsistence allowance staff in Dalian during two months in spring 2015. With the survey data, this study analyzed the matching degree between urban subsistence allowance of childrens welfare needs and its current assistance system in Dalian. As a result, this study provides the direction for development for urban subsistence allowance for childrens assistance system, especially with the perspective of providing assistance policy and service considering child developmental needs. There are three main results obtained in this research. First, in the Community Subsistence Allowance Staffs opinion, the most important five welfare needs are Childrens serious disease treatment charge (including medicine fee), High school tuition, High school stationary/course material fee, primary & middle & high school lunch fee, and Childrens office visit & hospitalization Fee(including medicine fee). Second, the current welfare policy and service in Dalian are urban residents' basic medical insurance, temporary assistance system, the program of China Charity Federation, High school financial aid, Vocational high school scholarship, and Temporary relief supplies. Third, as to matching the degree between the governmental welfare policy & service, most of the Community Subsistence Allowance Staffs had a positive attitude (39.5%) as the matched & well matched, while 27.9% of Community Subsistence Allowance Staffs chose the ordinary. However, the attitude to the matching degree between Urban Subsistence Allowance Children and the non-governmental relief showed only 11.0% of them to have a positive attitude, while 34.9% of them chose the ordinary as their answer. For welfare policy & servicethe items chosen in need to be added are sociability (Activities on campus), education (primary & middle & high school stationery relief), and care (after school& vacation care service). From the current welfare policy & service, they choose Health (Childrens office visit & hospitalization Fee, Childrens serious disease treatment charge) as the item which its scope of aid ought to be expanded. According to the analysis of the results, the policy & clinical significance are as follows. First, the subsistence allowance system, compulsory education system and the Urban residents' basic medical insurance, all current policies, only fulfill fundamental needs for urban subsistence allowance for children. Therefore, its supporting strength and aid ranges should be increased, especially for the Health and Education. For Health, the current range of relief disease category, financial aids limit ought to be expanded. For Education, school lunch fee, high school course material fee, uniform fee and so on should be funded. Second, as the most important supporting policy, the subsistence allowance system only provides the minimum living allowance based on the family unit and there is no support for children of subsistence allowance in the family. Therefore a support system that is fitting and considers child development characteristics should be implemented for future improvement. Third, at present, administration and regulations for urban subsistence allowance for children have not been established, thus standardized rules should be statured immediately. This study is an exploratory study, not only investigated the Urban Subsistence Allowance Childrens Welfare Needs and the information of childrens welfare need according to their development characteristics, but also analyzed the necessity to attach great importance to providing welfare policy & service matching to the childrens development characteristics rather than their basic living. Also, the results of this study is expected to be useful for reference to develop and perfect other citys Urban Subsistence Allowance Childrens Welfare system. Key Words: urban subsistence allowance system, children of urban subsistence allowance family, welfare needs, assistance system for children Student Number: 2012-23896๋ชฉ ์ฐจ ์ œ 1 ์žฅ ์„œ ๋ก  1 ์ œ 1 ์ ˆ ๋ฌธ์ œ์ œ๊ธฐ 1 ์ œ 2 ์ ˆ ์—ฐ๊ตฌ ๋ฌธ์ œ 5 ์ œ 3 ์ ˆ ์—ฐ๊ตฌ ๋ถ„์„ํ‹€ 6 ์ œ 2 ์žฅ ์ด๋ก ์  ๋ฐฐ๊ฒฝ 10 ์ œ 1 ์ ˆ ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์ œ๋„ 10 1. ์ตœ์ €์ƒํ™œ๋ณด์žฅ์ œ๋„์˜ ๊ฐœ๋… ๋ฐ ์ „๊ฐœ ๊ณผ์ • 10 2. ๋‹ค๋ก„์‹œ ์ตœ์ €์ƒํ™œ๋ณด์žฅ์ œ๋„ ํ˜„ํ™ฉ 11 ์ œ 2 ์ ˆ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™ 16 1. ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์˜ ์ •์˜ 16 2. ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™๊ณผ ๋ฐœ๋‹ฌ ๋ชจ๋ธ 17 ์ œ 3 ์ ˆ ๋ณต์ง€์š•๊ตฌ 25 1. ๋ณต์ง€์š•๊ตฌ์˜ ๊ฐœ๋… 25 2. ์ผ๋ฐ˜ ์•„๋™์˜ ๋ณต์ง€์š•๊ตฌ 26 3. ๋„์‹œ ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์˜ ๋ณต์ง€์š•๊ตฌ 27 ์ œ 4 ์ ˆ ์ค‘๊ตญ์˜ ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์„ ์œ„ํ•œ ๋ณต์ง€ ์ง€์› ํ˜„ํ™ฉ 35 ์ œ 3 ์žฅ ์—ฐ๊ตฌ ๋ฐฉ๋ฒ• 38 ์ œ 1 ์ ˆ ์ž๋ฃŒ์ˆ˜์ง‘ ๋ฐฉ๋ฒ• 38 ์ œ 2 ์ ˆ ์ž๋ฃŒ์ˆ˜์ง‘ ๋Œ€์ƒ์ž: ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์š”์›์˜ ํŠน์„ฑ 40 1. ์‚ฌํšŒ์ฃผ์˜ ์ง€์—ญ์‚ฌํšŒ์œ„์›ํšŒ์˜ ์„ฑ๊ฒฉ 40 2. ์ž๋ฃŒ์ˆ˜์ง‘ ๋Œ€์ƒ์ž๋กœ ์„ ์ •ํ•œ ๊ทผ๊ฑฐ 42 ์ œ 3 ์ ˆ ์ธํ„ฐ๋ทฐ ์งˆ๋ฌธ์ง€์˜ ๋ฌธํ•ญ๊ตฌ์„ฑ 44 ์ œ 4 ์ ˆ ์ž๋ฃŒ ๋ถ„์„ ๋ฐฉ๋ฒ• 47 ์ œ 4 ์žฅ ์กฐ์‚ฌ๊ฒฐ๊ณผ ๋ฐ ๋ถ„์„ 49 ์ œ 1 ์ ˆ ์ตœ์ €์ƒํ™œ๋ณด์žฅ ์š”์›์˜ ์ผ๋ฐ˜์  ํŠน์ง• 51 ์ œ 2 ์ ˆ ๋‹ค๋ก„์‹œ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์˜ ๋ณต์ง€์š•๊ตฌ 52 1. ์–‘์  ์ž๋ฃŒ ๋ถ„์„ 52 (1) ์ „๋ฐ˜์ ์ธ ๋ณต์ง€์š•๊ตฌ ํ•„์š”์„ฑ์— ๋Œ€ํ•œ ์ธ์‹ 52 (2)์ƒํƒœ์ฒด๊ณ„ํ•™์  ๋ชจ๋ธ์— ๋”ฐ๋ฅธ ๋ณต์ง€์š•๊ตฌ ํ•„์š”์„ฑ์˜ ์žฌ๋ถ„๋ฅ˜ 56 2. ์งˆ์  ์ž๋ฃŒ ๋ถ„์„ 58 ์ œ 3 ์ ˆ ๋‹ค๋ก„์‹œ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์„ ์œ„ํ•œ ๋ณต์ง€ ์ •์ฑ…๊ณผ ์„œ๋น„์Šค ํ˜„ํ™ฉ 65 1. ์–‘์  ์ž๋ฃŒ ๋ถ„์„ 65 (1) ๋‹ค๋ก„์‹œ์˜ ํ˜„ํ–‰ ๋ณต์ง€ ์ •์ฑ…๊ณผ ์„œ๋น„์Šค 66 2. ์งˆ์  ์ž๋ฃŒ ๋ถ„์„ 83 ์ œ 4 ์ ˆ ๋‹ค๋ก„์‹œ ๋„์‹œ ํ˜ธ์  ์ˆ˜๊ธ‰์ž ๊ฐ€๊ตฌ ์•„๋™์˜ ๋ณต์ง€์š•๊ตฌ์™€ ํ˜„ํ–‰ ๋ณต์ง€ ์ •์ฑ… ๋ฐ ์„œ๋น„์Šค์˜ ๋ถ€ํ•ฉ ์ •๋„ 95 1. ์–‘์  ์ž๋ฃŒ ๋ถ„์„ 95 (1) ๋ณต์ง€์š•๊ตฌ์™€ ํ˜„ํ–‰ ๋ณต์ง€ ์ •์ฑ… ๋ฐ ์„œ๋น„์Šค์˜ ๋ถ€ํ•ฉ ์ •๋„์— ๋Œ€ํ•œ ์ธ์‹ 95 (2) ์‹คํ–‰ ๋˜๋Š” ํ™•๋Œ€๊ฐ€ ํ•„์š”ํ•œ ๋ณต์ง€ ์ •์ฑ…/์„œ๋น„์Šค 97 2. ์งˆ์  ์ž๋ฃŒ ๋ถ„์„ 101 ์ œ 5 ์žฅ ๊ฒฐ๋ก  118 ์ œ 1 ์ ˆ ์ฃผ์š” ์—ฐ๊ตฌ๊ฒฐ๊ณผ 118 ์ œ 2 ์ ˆ ์—ฐ๊ตฌ์˜ ํ•œ๊ณ„ 128 ์ œ 3 ์ ˆ ์—ฐ๊ตฌ์˜ ํ•จ์˜ ๋ฐ ์ œ์•ˆ 130 ์ฐธ๊ณ ๋ฌธํ—Œ 137 ์ธํ„ฐ๋ทฐ ์งˆ๋ฌธ์ง€ ํ•œ๊ตญ์–ด 146 ์ธํ„ฐ๋ทฐ ์งˆ๋ฌธ์ง€ ์ค‘๊ตญ์–ด 154 ๆ‘˜่ฆ 161 Abstract 164Maste

    p53/miRNA-34 Axis์— ์˜ํ•œ CD44 ๋ฐœํ˜„๊ณผ ์•” ์ „์ด ์กฐ์ ˆ

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    Dept. of Dental science/๋ฐ•์‚ฌCD44 is a transmembrane glycoprotein involved in cell-cell and cell-matrix adhesion and in cell migration. This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Recent study reveals that CD44 plays an important role in regulation of cancer stem cells. P53 tumor suppressor is the key player at the center of a complex molecular network regulating diverse cancer related pathways. MiRNA are short non-coding RNAs, on average only 22 nucleotides long, which interact with complementary or near-complementary matched sites in the untranslated regions (UTRs) of mRNA targets. It is a vital and evolutionarily ancient component of genetic regulation and can have tumor suppressor or oncogenic activity. The previous studies on miRNA-34 family induced by p53 activation had focus on the function of cell cycle arrest, apoptosis. But the relationship of the p53/miRNA-34 tumor suppressor network and cancer stem cells remains unclear.In this study, we showed miR-34 family''s direct target sites on CD44 by the bioinformatic prediction, which lie in 3'' UTR and 5'' UTR. We also examined the Regulation of CD44 by p53-miR34 tumor suppressor network and the role of CD44 in cancer migration and invasion. The results are as follows:1. The miRNA-34 family has target sites on 3โ€™ UTR and 5โ€™ UTR of CD44 simultaneously.2. CD44 is highly expressed in A549 cells and MDA-MB 231 cells.3. Loss of p53 function and p53 degradation potentiate CD44 protein expression and 3โ€™ UTR and 5โ€™ UTRโ€™s activity. 4. CD44 is a direct target of miRNA-34.5. MiRNA-34 inhibits CD44-mediated cancer cell migration and invasion.The results of the study provide insight into the mechanisms by which p53/miR-34 axis restrains CD44, and suggest the therapeutic strategy in cancer stem cells.ope

    ์ผ์ œ์˜ 'ๅ…ง้ฎฎ็ตๅฉš' ์ •์ฑ…

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ๊ตญ์‚ฌํ•™๊ณผ, 2015. 2. ๊ถŒํƒœ์–ต.๋ณธ๊ณ ๋Š” ์ผ์ œํ•˜ ์ผ๋ณธ์ธ๊ณผ ์กฐ์„ ์ธ์˜ ๊ฒฐํ˜ผ, ์ฆ‰ ๅ…ง้ฎฎ็ตๅฉš์— ๋Œ€ํ•œ ์ •์ฑ…์„ ํ†ตํ˜ผ์˜ ์‹ค์ œ ์–‘์ƒ๊ณผ ํ•จ๊ป˜ ๋ถ„์„ํ•จ์œผ๋กœ์จ, ์–‘ ๋ฏผ์กฑ์˜ ์ธ์ข…์  ์œ ์‚ฌ์„ฑ์„ ์ „์ œ๋กœ ํ•œ ์ผ์ œ์˜ ์กฐ์„ ์ธ ๋™ํ™”์ •์ฑ…์ด ๋™์š”โ€คํฌ๊ธฐ๋˜์–ด๊ฐ€๋Š” ๊ณผ์ •์„ ์‚ดํŽด๋ณธ ์—ฐ๊ตฌ์ด๋‹ค. ์„œ๊ตฌ์˜ ๋ฐฑ์ธ์ข…์ด ์•„์‹œ์•„โ€ค์•„ํ”„๋ฆฌ์นด์˜ ์œ ์ƒ‰ ์ธ์ข…์„ ์‹๋ฏผ์ง€๋ฐฐํ•˜๋Š” ๊ฒƒ์ด ์ผ๋ฐ˜์ ์ธ ๊ฐ€์šด๋ฐ, ์ผ์ œ๋Š” ๊ฐ™์€ ํ™ฉ์ธ์ข…์ธ ๋Œ€๋งŒ์ธ๊ณผ ์กฐ์„ ์ธ์„ ์ง€๋ฐฐํ–ˆ๋‹ค. ๋‹น์‹œ ์„œ๊ตฌ์—์„œ๋Š” ์ธ์ข…์ฃผ์˜๊ฐ€ ๋ฐœํฅํ•˜๋ฉด์„œ ์‹๋ฏผ์ง€๋ฏผ๊ณผ์˜ ๊ฒฐํ˜ผ์„ ์žฅ๋ คํ•˜๋˜ ์ •์ฑ…์„ ํ๊ธฐํ•˜๊ฑฐ๋‚˜ ์•„์˜ˆ ํ†ตํ˜ผ์„ ๊ธˆ์ง€ํ•˜๊ณ  ๋™ํ™”์ •์ฑ…๋„ ์ ์ฐจ ํฌ๊ธฐํ•˜๋Š” ์ถ”์„ธ์˜€์ง€๋งŒ, ์ผ์ œ๋Š” ์ผ๋ณธ์ธ๊ณผ ์กฐ์„ ์ธ์€ ์ธ์ข…์ ์œผ๋กœ ์œ ์‚ฌํ•˜๊ธฐ ๋•Œ๋ฌธ์— ๋™ํ™”ํ•  ์ˆ˜ ์žˆ๋‹ค๊ณ  ๋ณด์•˜๋‹ค. ๋”๊ตฐ๋‹ค๋‚˜ ๊ณ ๋Œ€๋ถ€ํ„ฐ ์ด๋ฏธ ํ†ตํ˜ผ ์‚ฌ๋ก€๊ฐ€ ํ’๋ถ€ํ–ˆ๋˜ ์กฐ์„ ์ธ๊ณผ์˜ ๊ฒฐํ˜ผ์„ ๋ง‰์„ ์ด์œ ๋Š” ์—†๊ณ , ํ†ตํ˜ผ์ด ์ฆ๊ฐ€ํ•˜๋ฉด ๋™ํ™”๋„ ์ด‰์ง„๋  ๊ฒƒ์œผ๋กœ ๊ธฐ๋Œ€ํ–ˆ๋‹ค. ๊ทธ๋Ÿฐ๋ฐ ๋ณ‘ํ•ฉ ์งํ›„์˜ ๋ฌธ์ œ๋Š” ์‹๋ฏผ์ง€ ์กฐ์„ ์— ์ผ๋ณธ ๋ณธํ† ์™€๋Š” ๋‹ค๋ฅธ ๋ฒ•๋ น์„ ์‹œํ–‰ํ•œ ๊ฒฐ๊ณผ, ์กฐ์„ ์—์„œ ํ˜ผ์ธ ์‹ ๊ณ ๋ฅผ ํ•ด์•ผ ํ•˜๋Š” ์กฐ์„ ์ธ ๋‚จ์„ฑ๊ณผ ์ผ๋ณธ์ธ ์—ฌ์„ฑ์˜ ๋ฒ•๋ฅ ํ˜ผ์ด ์„ฑ๋ฆฝํ•  ์ˆ˜ ์—†๊ฒŒ ๋œ ๊ฒƒ์ด์—ˆ๋‹ค. ์ด๋Š” ์ด๋ฏธ ์ž์—ฐ์Šค๋Ÿฝ๊ฒŒ ์ด๋ฃจ์–ด์ง€๊ณ  ์žˆ๋˜ ๋‚ด์„ ๊ฒฐํ˜ผ์„ ๊ธˆ์ง€ํ•˜๋Š” ๊ฒƒ์ฒ˜๋Ÿผ ๋ณด์—ฌ ์กฐ์„ ์ธ์˜ ๋ฐ˜๊ฐ์„ ๋ถˆ๋Ÿฌ์ผ์œผํ‚ฌ ์šฐ๋ ค๊ฐ€ ์žˆ์—ˆ์„ ๋ฟ ์•„๋‹ˆ๋ผ, ่ค‡ๆœฌ็ฑ๊ณผ ้‡ๅฉš๊นŒ์ง€ ์•ผ๊ธฐํ–ˆ๋‹ค. ์ผ์ œ๋Š” ๋‚ด์„ ๊ฒฐํ˜ผํ•˜๋ ค๋Š” ์‚ฌ๋žŒ๋“ค์„ ๋ง‰์„ ์ˆ˜๋„, ๋ง‰์„ ์ƒ๊ฐ๋„ ์—†์—ˆ์ง€๋งŒ, ๋ณ‘ํ•ฉ ์ดˆ๊ธฐ์ธ 1910๋…„๋Œ€์—๋Š” ์ œ๋„์  ๊ฒฐํ•จ์ด ์žˆ์—ˆ๋˜ ๊ฒƒ์ด๋‹ค. ๋‚ด์„ ๊ฒฐํ˜ผ์„ ๋ฒ•์ ์œผ๋กœ ์ธ์ •ํ•˜๋Š” ๋ฐ๋Š” ์กฐ์„ ์ด๋…๋ถ€๊ฐ€ ๋” ์ ๊ทน์ ์ด์–ด์„œ, ๅ…ฑ้€šๆณ•(1918) ์ œ์ • ๊ณผ์ •์—์„œ๋Š” ๊ฑฐ์ฃผ ์ง€์—ญ์ด๋‚˜ ๋ฏผ์กฑ, ์„ฑ์— ๋”ฐ๋ฅธ ๊ตฌ๋ณ„ ์—†์ด ํ†ตํ˜ผ์˜ ์ž์œ ๋ฅผ ์ธ์ •ํ•˜๋„๋ก ์ผ๋ณธ ์ •๋ถ€๋ฅผ ์„ค๋“ํ–ˆ๊ณ , ๋ฒ•๋ฅ ์˜ ์‹œํ–‰ ์‹œ๊ธฐ๋ฅผ ์•ž๋‹น๊ธฐ๊ธฐ ์œ„ํ•ด ์กฐ์„ ์˜ ํ˜ธ์ ์ œ๋„๋„ ์ •๋น„ํ–ˆ๋‹ค. ๊ทธ๋ฆฌํ•˜์—ฌ ์กฐ์„ ์ธ๊ณผ ์ผ๋ณธ์ธ์€ 1921๋…„ 7์›”๋ถ€ํ„ฐ ๋ฒ•๋ฅ ํ˜ผ์„ ์˜จ์ „ํžˆ ํ•  ์ˆ˜ ์žˆ๊ฒŒ ๋˜์—ˆ๋‹ค. 1919๋…„ 3โ€ค1 ์šด๋™ ์ดํ›„ ์กฐ์„ ์ธ์˜ ๋ฏผ์‹ฌ์„ ์ˆ˜์Šตํ•ด์•ผ ํ–ˆ๋˜ ์กฐ์„ ์ด๋…๋ถ€๋Š” ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ๋ฅผ ๋ฌด์ฐจ๋ณ„์˜ ์ฆ๊ฑฐ๋กœ ์ ๊ทน ์„ ์ „ํ•˜๋ฉด์„œ, ํ˜ธ์ ์œผ๋กœ ๋ฏผ์กฑ์„ ๊ตฌ๋ณ„ํ•˜๋Š” ์‹ค์งˆ์ ์ธ ์ฐจ๋ณ„์„ ๋ถ€์ฐจ์ ์ธ ๊ฒƒ์œผ๋กœ ์น˜๋ถ€ํ–ˆ๋‹ค. ํ•˜์ง€๋งŒ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ์˜ ์‹œํ–‰์œผ๋กœ ์ œ๊ตญ ์ผ๋ณธ ๋‚ด ๋ณต๋ณธ์ ๊ณผ ์ค‘ํ˜ผ์˜ ๋ฌธ์ œ๋„ ์ œ๊ฑฐ๋˜์—ˆ๋‹ค. ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ๋Š” ๋™ํ™”์˜ ์ด๋…์— ๋ถ€ํ•ฉํ•˜๋„๋ก ํ†ตํ˜ผ์„ ์ž์œ ๋กญ๊ฒŒ ๋งŒ๋“œ๋Š” ๋™์‹œ์—, ์ œ๊ตญ ์ผ๋ณธ์˜ ๋ฒ•์  ์งˆ์„œ๋ฅผ ์•ˆ์ •์‹œํ‚ค๋Š” ์—ญํ• ์„ ํ•œ ๊ฒƒ์ด๋‹ค. ํ•˜์ง€๋งŒ ์ด๋กœ ์ธํ•ด ๋‚ด์„ ๊ฒฐํ˜ผ์€ ์กฐ์„ ์ธ์ด ์ผ๋ณธ์ธ์œผ๋กœ, ์ผ๋ณธ์ธ์ด ์กฐ์„ ์ธ์œผ๋กœ ํ˜ธ์ ์ƒ ์‹ ๋ถ„์„ ๋ฐ”๊ฟ€ ์ˆ˜ ์žˆ๋Š” ์œ ์ผํ•œ ๊ธธ์ด๋ฉด์„œ๋„, ์‹ ๊ณ ๋งŒ์œผ๋กœ ์„ฑ๋ฆฝํ•˜๊ฒŒ ๋˜์—ˆ๋‹ค. ๊ฒŒ๋‹ค๊ฐ€ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ๋Š” 1923๋…„ 7์›”๋ถ€ํ„ฐ ๅ…ฅ้คŠ, ่ช็Ÿฅ, ่ฆชๆ—ๅ…ฅ็ฑ์—๋„ ์ ์šฉ๋˜๋Š” ๋“ฑ, ํ˜ธ์ ์„ ๋ณ€๊ฒฝํ•  ์ˆ˜ ์žˆ๋Š” ๋ฒ”์œ„๋Š” ์ ์ฐจ ํ™•๋Œ€๋˜์—ˆ๋‹ค. ๊ทธ๋Ÿฌ์ž ์ด๋ฅผ ์ด์šฉํ•ด ๋ฒ•์ ์œผ๋กœ ์ผ๋ณธ์ธ์ด ๋˜๋ ค๋Š” ์กฐ์„ ์ธ๋„ ๋‚˜ํƒ€๋‚ฌ๊ณ , ๊ฒฐ๊ณผ์ ์œผ๋กœ ์กฐ์„  ํ˜ธ์ ์—๋Š” ์ผ๋ณธ์ธ ์—ฌ์„ฑ์ด, ์ผ๋ณธ ํ˜ธ์ ์—๋Š” ์กฐ์„ ์ธ ๋‚จ์„ฑ์ด ์ฃผ๋กœ ์ž…์ ํ–ˆ๋‹ค. ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ๋Š” ๋ฌด์ฐจ๋ณ„์˜ ์ง•ํ‘œ์ธ ๋งŒํผ ์ผ์ œ๋Š” ๊ทธ๋กœ ์ธํ•œ ํ˜ธ์  ์ด๋™๋„ ์ตœ๋Œ€ํ•œ ํ—ˆ์šฉํ–ˆ์ง€๋งŒ, ์ผ๋ฐ˜์ธ๋“ค์˜ ํ–‰๋™์— ๋ฐฉ์ž„๋œ ๊ทธ ๊ฒฐ๊ณผ๋Š” ๋‹น๊ตญ์˜ ๊ธฐ๋Œ€์™€๋Š” ๋‹ฌ๋ž๋˜ ๊ฒƒ์ด๊ณ , ํ†ตํ˜ผ์ด ์ฆ๊ฐ€ํ•˜๋ฉด ํ˜ธ์ ์œผ๋กœ ๋ฏผ์กฑ์„ ๊ตฌ๋ณ„ํ•˜๋Š” ์ œ๊ตญ ๋ฒ•์ œ๊ฐ€ ๋™์š”ํ•  ์šฐ๋ ค๋งˆ์ € ์žˆ์—ˆ๋‹ค. ์กฐ์„ ์ด๋…๋ถ€๋Š” ๋‚ด์„ ๊ฒฐํ˜ผ์˜ ๋ฒ•๋ฅ ํ˜ผ์ด ๊ฐ€๋Šฅํ•ด์ง„ 1921๋…„์„ ์ „ํ›„ํ•˜์—ฌ, ๋‚ด์„ ๊ฒฐํ˜ผ์„ ์กฐ์„ ์ธ๊ณผ ์ผ๋ณธ์ธ์ด ์„œ๋กœ ์‚ฌ๋ž‘ํ•œ ๊ฒฐ๊ณผ์ด์ž ๊ทธ ์‚ฌ๋ž‘์„ ๊ฐ€์กฑ๊ณผ ์‚ฌํšŒ์— ์—ฐ์‡„์‹œ์ผœ ์–‘ ๋ฏผ์กฑ์˜ ์˜๊ตฌ๊ฒฐํ•ฉ์„ ๊ฐ€์ ธ์˜ฌ ์ˆ˜๋‹จ์œผ๋กœ ๋ถ€๊ฐ์‹œ์ผฐ๋‹ค. ๊ทธ๋ฆฌ๊ณ  ๋ฒ•๋ฅ ํ˜ผ๊ณผ ๅ…ง็ทฃ์„ ๋ถˆ๋ฌธํ•˜๊ณ  ์กฐ์„ ์—์„œ ๋™๊ฑฐํ•˜๋Š” ๋‚ด์„ ๊ฒฐํ˜ผ ๋ถ€๋ถ€์˜ ํ†ต๊ณ„๋ฅผ ๊ณตํ‘œํ•˜๋ฉด์„œ, ๋ถ€๋ถ€ ์ˆ˜์˜ ์ฆ๊ฐ€๊ฐ€ ๅ…ง้ฎฎ่žๅ’Œ์˜ ์ฆ์ง„์„ ์˜๋ฏธํ•œ๋‹ค๊ณ  ์„ ์ „ํ–ˆ๋‹ค. ํ•˜์ง€๋งŒ ๋ณด์กฐ๊ธˆ์„ ์ง€๊ธ‰ํ•˜๋Š” ๋“ฑ ํ†ตํ˜ผ์„ ์‹ค์งˆ์ ์œผ๋กœ ์ด‰์ง„ํ•  ์ˆ˜๋‹จ์€ ์‹œํ–‰ํ•˜์ง€ ์•Š์•˜๋Š”๋ฐ, ๋ฒ•๋ฅ ํ˜ผ์˜ ๊ธ‰์ฆ์€ ์ œ๊ตญ ๋ฒ•์ œ์˜ ์œ„ํ—˜ ์š”์†Œ์˜€์„ ๋ฟ ์•„๋‹ˆ๋ผ, ํ†ตํ˜ผ์„ ๊ธˆ์ง€ํ•˜๋Š” ๊ฒƒ๋งŒํผ์ด๋‚˜ ์ ๊ทน ์žฅ๋ คํ•˜๋Š” ๊ฒƒ๋„ ์กฐ์„ ์ธ์˜ ๋ฐ˜๋ฐœ์„ ์•ผ๊ธฐํ•  ์šฐ๋ ค๊ฐ€ ์žˆ์—ˆ๊ธฐ ๋•Œ๋ฌธ์œผ๋กœ ๋ณด์ธ๋‹ค. ์ด์— ์กฐ์„ ์ด๋…๋ถ€๋Š” ์„ ์ „์„ ๊ฐ•ํ™”ํ•˜์—ฌ ๋‚ด์„ ๊ฒฐํ˜ผ์„ ๋ฐฉํ•ดํ•˜๋Š” ์‚ฌํšŒํ†ต๋…์„ ์ œ๊ฑฐํ•˜๋Š” ์†Œ๊ทน์ โ€ค๊ฐ„์ ‘์  ์žฅ๋ ค์ •์ฑ…์„ ์ทจํ•˜๋Š” ๋ฐ ๊ทธ์ณค๋‹ค. ํ•˜์ง€๋งŒ ์ด๋กœ์จ ํ˜„์‹ค์— ๋ฐฉ์ž„๋œ ๋‚ด์„ ๊ฒฐํ˜ผ์˜ ์ฆ๊ฐ€ ์†๋„๋Š” ๋ฏธ๋ฏธํ–ˆ๊ณ , ์œ ํ˜•โ€ค๊ฑฐ์ฃผ์ง€โ€ค์ง์—…์— ๋”ฐ๋ฅธ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ถ€๋ถ€ ์ˆ˜์˜ ๋ถˆ๊ท ํ˜•์€ ์˜คํžˆ๋ ค ์กฐ์„ ์ธ์ด ์ผ๋ณธ์ธ๋ณด๋‹ค ์—ด๋“ฑํ•œ ์ง€์œ„์— ๋†“์—ฌ ์žˆ์Œ์„ ๋ฐ˜์ฆํ•˜๊ธฐ๋„ ํ–ˆ๋‹ค. ๋‹ค๋งŒ, ๋‚จ์„ฑ์˜ ๋‹จ์‹  ์ด์ฃผ์™€ ๋ฏผ์กฑ ๊ฐ„ ์ ‘์ด‰ ๊ธฐํšŒ์˜ ์ฆ๊ฐ€๋ฅผ ๋ฐ˜์˜ํ•˜์—ฌ, 1920๋…„๋Œ€ ์ดํ›„ ๋‚ด์„ ๊ฒฐํ˜ผ์˜ ์ ˆ๋Œ€ ์ˆ˜๋Š” ์ฆ๊ฐ€ํ•˜๊ณ  ์žˆ์—ˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ์„ ์ „๊ณผ ๋‹ฌ๋ฆฌ, ์ •๋žต๊ฒฐํ˜ผ์ด๋‚˜ ๊ฒฝ์ œ์  ๋™๊ธฐ๋กœ ์ธํ•œ ๊ฒฐํ˜ผ๋„ ์ƒ๋‹นํ–ˆ๊ณ , ์กฐ์„ ์ธ ๋˜๋Š” ์ผ๋ณธ์ธ์ž„์„ ์†์ด๋Š” ์‹ ๋ถ„ ์‚ฌ๊ธฐ๋‚˜ ์„ฑ๋ฒ”์ฃ„, ์ธ์‹ ๋งค๋งค ๋“ฑ์ด ํ†ตํ˜ผ์˜ ๋™๊ธฐ๊ฐ€ ๋˜๊ธฐ๋„ ํ–ˆ๋‹ค. ๋ฌผ๋ก  ๋‚ด์„ ๊ฒฐํ˜ผ์˜ ์ฃผ๋œ ๋™๊ธฐ๋Š” ์ž์œ ์—ฐ์• ์˜€์ง€๋งŒ, ์‚ฌ๋ž‘์€ ์˜์›ํ•˜์ง€ ์•Š๊ณ  ๊ฒฐ๋ณ„โ€ค์ดํ˜ผ์œผ๋กœ ๊ท€๊ฒฐ๋˜๊ฑฐ๋‚˜ ์ถ•์ฒฉโ€ค๊ฐ„ํ†ต์œผ๋กœ ๋ฐœํ˜„๋˜๋Š” ๋“ฑ ๋‚ด์„ ์—ฐ์• ์™€ ๋‚ด์„ ๊ฒฐํ˜ผ์€ ๊ฐ์ข… ์‚ฌ๊ฑด์‚ฌ๊ณ ์™€ ๊ฐ€์ •๋ถˆํ™”๋ฅผ ๋™๋ฐ˜ํ–ˆ๋‹ค. ๋˜ํ•œ ๋‚ด์„ ๊ฒฐํ˜ผ์„ ๋ฐฑ์•ˆ์‹œํ•˜๋Š” ๋ถ€๋ชจโ€ค์นœ์ง€๋‚˜ ์‚ฌํšŒ๊ฐ€ ํ†ตํ˜ผ ๋ถ€๋ถ€์™€ ๊ทธ ์ž๋…€๋“ค์„ ์†Œ์™ธ์‹œํ‚ค๋Š” ๋“ฑ, ํ†ตํ˜ผ ๊ฐ€์ •์€ ํŒŒํƒ„์— ์ด๋ฅด๊ธฐ๋„ ์‰ฌ์› ๋‹ค. ์กฐ์„ ์ด๋…๋ถ€๋Š” ๋‚ด์„ ์œตํ™”์˜ ์ƒ์ง•์ธ ๋‚ด์„ ๊ฒฐํ˜ผ ๊ฐ€์ •์ด ๋ชจ๋‘ ์›๋งŒโ€คํ™”๋ชฉํ•˜๊ฒŒ ์ƒํ™œํ•œ๋‹ค๊ณ  ์„ ์ „ํ–ˆ์ง€๋งŒ, ํ†ตํ˜ผ์ด ํ™•์‚ฐ๋จ์— ๋”ฐ๋ผ ๋ถˆํ™”๋ฅผ ๋™๋ฐ˜ํ•œ ๊ทธ ์‹ค์ƒ๋„ ์ผ๋ฐ˜์— ์•Œ๋ ค์ง€๋ฉด์„œ ๋‚ด์„ ์œตํ™”์˜ ๊ธฐ๋ฐ˜์ด ์ทจ์•ฝํ•จ์„ ๋“œ๋Ÿฌ๋‚ธ ๊ฒƒ์ด๋‹ค. ์ด๋•Œ ์ •๋žต์ ์œผ๋กœ ๊ฒฐํ˜ผํ–ˆ๊ฑฐ๋‚˜ ๊ฒฝ์ œ์ ์œผ๋กœ ์•ˆ์ •๋œ ์ƒ์ธต์˜ ๋‚ด์„ ๊ฒฐํ˜ผ ๊ฐ€์ •์€ ๋น„๊ต์  ์˜ค๋ž˜ ์œ ์ง€๋˜๋Š” ํŽธ์ด์—ˆ๊ณ , ์กฐ์„ ์ธ ๋‚จํŽธ์ด ๋™ํ™”๋˜๋ ค๋Š” ์˜์ง€๊ฐ€ ๊ฐ•ํ•œ ๊ฒฝ์šฐ ์ƒํ™œ์–‘์‹๋„ ์ผ๋ณธํ™”๋˜์—ˆ๋‹ค. ํ•˜์ง€๋งŒ ๊ทธ ์™ธ ์กฐ์„ ์— ๊ฑฐ์ฃผํ•˜๋Š” ํ†ตํ˜ผ ๊ฐ€์ •๋“ค์€ ๋Œ€๊ฐœ ํŽธ์˜๋ฅผ ์œ„ํ•ด์„œ๋ผ๋„ ์–ด๋Š ์ •๋„ ์กฐ์„ ์˜ ์ƒํ™œ์–‘์‹์„ ์ˆ˜์šฉํ–ˆ๊ณ , ์‹œ๋Œ์— ์ˆœ์ข…ํ•ด ์กฐ์„ ์ธํ™”๋œ ์ผ๋ณธ์ธ ์ฒ˜๋„ ๋งŽ์•˜๋‹ค. ์กฐ์„ ์ด๋…๋ถ€๋Š” ๋‚ด์„ ๊ฒฐํ˜ผ์ด ์กฐ์„ ์ธ์˜ ์‚ฌ์ƒ๊ณผ ์ƒํ™œ์–‘์‹์„ ์ผ๋ณธ์ธํ™”ํ•˜๊ณ  ์ž๋…€๋ฅผ ๋‚ณ์•„ ํ”ผ์™€ ์œก์ฒด๊นŒ์ง€ ํ•˜๋‚˜๋กœ ๋งŒ๋“œ๋Š” ๊ถ๊ทน์  ๋™ํ™”๋ฅผ ๊ฐ€์ ธ์˜ฌ ๊ฒƒ์ด๋ผ๊ณ  ์„ ์ „ํ–ˆ์ง€๋งŒ, ์—ญ์œผ๋กœ ์ผ๋ณธ์ธ๋„ ์กฐ์„ ํ™”์‹œํ‚จ ๊ฒƒ์ด๋‹ค. ์กฐ์„ ์ด๋…๋ถ€๋Š” ํ†ตํ˜ผ์˜ ํ™•์‚ฐ์ด ์–‘ ๋ฏผ์กฑ์˜ ๋ถˆํ™”๋ฅผ ๋…ธ์ •ํ•˜๊ณ  ์กฐ์„ ์ธ์„ ์ผ๋ณธ์ธํ™”ํ•˜๋Š” ํšจ๊ณผ๋„ ํฌ์ง€ ์•Š์Œ์„ ์ธ์‹ํ•˜๊ณ , 1930๋…„๋Œ€ ์ค‘ํ›„๋ฐ˜๊ฒฝ๋ถ€ํ„ฐ๋Š” ๋‚ด์„ ๊ฒฐํ˜ผ์„ ๋™ํ™”์˜ ์ˆ˜๋‹จ์ด ์•„๋‹ˆ๋ผ ๊ฒฐ๊ณผ๋กœ ์ดํ•ดํ•˜๋Š” ์‹œ๊ฐ์ด ๊ฐ•ํ•ด์กŒ๋‹ค. ์กฐ์„ ์ธ ์ „๋ฐ˜์ด ๋™ํ™”๋˜๊ธฐ ์ „๊นŒ์ง€๋Š” ํ†ตํ˜ผ์„ ๋„๋ฆฌ ํ™•์‚ฐ์‹œํ‚ค๊ธฐ๋ณด๋‹ค ์ƒ์ธต ์กฐ์„ ์ธ ์œ„์ฃผ๋กœ ๋ชจ๋ฒ”์ ์ด๊ณ  ์•ˆ์ •์ ์ธ ๊ฐ€์ •์ด ํ˜•์„ฑ๋˜๋Š” ํŽธ์ด ๋ฐ”๋žŒ์งํ•˜๋‹ค๊ณ  ์ƒ๊ฐํ•œ ๊ฒƒ์ด๋‹ค. ์ด์— ์ „์‹œ์ฒด์ œ๊ธฐ์—๋Š” ์กฐ์„ ์ธ์„ ๋™์›ํ•˜๊ธฐ ์œ„ํ•ด ์ •์‹ ์ โ€ค๋ฌธํ™”์  ๋™ํ™”์— ๋ฐ•์ฐจ๋ฅผ ๊ฐ€ํ•˜๋ฉด์„œ๋„ ๋‚ด์„ ๊ฒฐํ˜ผ์— ๋Œ€ํ•ด์„œ๋Š” ๋ฒ•์  ์ œ์•ฝ์„ ์ถ•์†Œํ•˜๊ณ  ์„ ์ „์„ ๊ฐ•ํ™”ํ•˜๋Š” ๋“ฑ ์†Œ๊ทน์ ์œผ๋กœ ์žฅ๋ คํ•˜๋Š” ์ •๋„์— ๊ทธ์ณค๋‹ค. ๋‚˜์•„๊ฐ€ ์ผ๋ณธ ์ •๋ถ€๋Š” ๋‚ด์„ ๊ฒฐํ˜ผ ์žฅ๋ ค์ •์ฑ… ์ž์ฒด๋ฅผ ๊ทผ๋ณธ์ ์œผ๋กœ ์žฌ๊ฒ€ํ† ํ–ˆ๋‹ค. ๊ทธ๊ฐ„ ์ƒ๋Œ€์ ์œผ๋กœ ํ†ตํ˜ผ์— ๋ฌด๊ด€์‹ฌํ–ˆ๋˜ ์ผ๋ณธ ์ •๋ถ€๊ฐ€ ๋ฏผ๊ฐํ•˜๊ฒŒ ๋ฐ˜์‘ํ•œ ์ด์œ ๋Š” ๋…ธ๋ฌด๋™์›๋œ ์กฐ์„ ์ธ ๋‚จ์„ฑ๊ณผ ์ผ๋ณธ์ธ ์—ฌ์„ฑ์˜ ๋‚ด์„ ๊ฒฐํ˜ผ์ด ๊ธ‰์ฆํ•˜์—ฌ ํ†ตํ˜ผ ๊ฐ€์ •์˜ ์ ˆ๋Œ€ ๋‹ค์ˆ˜๊ฐ€ ์ผ๋ณธ ๋ณธํ† ์— ๊ฑฐ์ฃผํ•˜๊ฒŒ ๋˜์—ˆ๊ธฐ ๋•Œ๋ฌธ์ด๋‹ค. ๋˜ํ•œ ์–‘์งˆ์˜ ์ธ์ ์ž์› ํ™•๋ณด๊ฐ€ ๆˆฐๆ™‚ไธ‹ ์ฃผ์š” ์ •์ฑ… ๊ณผ์ œ๊ฐ€ ๋˜์ž, ํ˜ผํ˜ˆ์ด ์ผ๋ณธ์ธ์˜ ์ •์‹ ๊ณผ ์‹ ์ฒด์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์— ๋Œ€ํ•ด์„œ๋„ ๊ด€์‹ฌ์ด ๋†’์•„์กŒ๊ธฐ ๋•Œ๋ฌธ์ด์—ˆ๋‹ค. ์ด์— ์ผ๋ณธ ์ •๋ถ€๋Š” ์ƒ๋ฌผํ•™์  ์ธ์ข…์ฃผ์˜๋ฅผ ๊ทผ๊ฑฐ๋กœ ํ•œ ๋™ํ™”์ •์ฑ… ๋ฐ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฐ˜๋Œ€๋ก ์„ ๊ณต์‹์ ์œผ๋กœ ๋ฐฐ๊ฒฉํ•˜๋ฉด์„œ๋„, ์šฐ์ƒํ•™์„ ๋ฐ”ํƒ•์œผ๋กœ ๋‚ด์„ ํ˜ผํ˜ˆ์•„์˜ ํŠน์ง• ๋ฐ ์ผ๋ณธ์— ๊ฑฐ์ฃผํ•˜๋Š” ํ†ตํ˜ผ ๊ฐ€์ •์˜ ์‹คํƒœ๋ฅผ ์ข…ํ•ฉ์ ์œผ๋กœ ์กฐ์‚ฌโ€ค์—ฐ๊ตฌํ•˜๊ธฐ ์‹œ์ž‘ํ–ˆ๋‹ค. ๊ทธ๋ฆฌ๊ณ  ๊ทธ ๊ฒฐ๊ณผ๋Š” ๋‚ด์„ ํ˜ผํ˜ˆ์•„๋Š” ์‹ ์ฒด์ ์œผ๋กœ๋Š” ๋ฌธ์ œ๊ฐ€ ์—†์ง€๋งŒ ๊ตญ๋ฏผ์˜์‹์ด ๋ฐ•์•ฝํ•˜๊ณ , ์žฌ์ผ์กฐ์„ ์ธ์€ ๋Œ€๊ฐœ ํ•˜์ธต ๋…ธ๋™์ž์ด๋ฏ€๋กœ ํ†ตํ˜ผ ๊ฐ€์ •๋„ ์—ด๋“ฑํ•˜๋‹ค๋Š” ๊ฒƒ์ด์—ˆ๋‹ค. ๋”ฐ๋ผ์„œ ์กฐ์„ ์—์„œ๋Š” ํ™ฉ๋ฏผํ™”๋œ ์ƒ์ธต ์กฐ์„ ์ธ๊ณผ ์ผ๋ณธ์ธ์ด ๊ฒฐํ˜ผํ•˜๋„๋ก ์ง€๋„ํ•ด๋„ ๋ฌด๋ฐฉํ•˜์ง€๋งŒ, ์ผ๋ณธ์—์„œ๋Š” ๋‚ด์„ ๊ฒฐํ˜ผ์— ์‹ ์ค‘ํ•ด์•ผ ํ•œ๋‹ค๋Š” ๊ฒฌํ•ด๊ฐ€ ๋Œ€์„ธ์˜€๋‹ค. ์ผ๋ณธ ์ •๋ถ€๋Š” ์ „์‹œ์ฒด์ œ๊ธฐ ๋‚ด์„ ๊ฒฐํ˜ผ๊ณผ ํ˜ผํ˜ˆ์ด ๋ณธํ† ์˜ ๋ฌธ์ œ๊ฐ€ ๋˜๊ณ , ์ผ๋ณธ์ธ ์—ฌ์„ฑ์ด ์กฐ์„ ์ธ ๋‚จ์„ฑ์˜ ์ฒ˜์ฒฉ์ด ๋˜๋Š” ๊ฒฝ์šฐ๊ฐ€ ๋Œ€๋ถ€๋ถ„์ธ ๋“ฑ ์ผ๋ณธ์ธ์˜ ์ž์กด๊ฐ๊นŒ์ง€ ํ›ผ์†ํ•˜์ž, ๊ตญ๋ฏผ์˜์‹๊ณผ ๊ณ„์ธต์„ ๊ทผ๊ฑฐ๋กœ ์ผ๋ณธ์—์„œ์˜ ํ†ตํ˜ผ์„ ๋ถ€์ •ํ•œ ๊ฒƒ์ด๋‹ค. ์ด๋Ÿฌํ•œ ํšŒ์˜์  ์‹œ๊ฐ์€ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ ์ด์™ธ์— ์กฐ์„ ์ธ์ด ์ผ๋ณธ์— ่ฝ‰็ฑํ•  ์ˆ˜ ์žˆ๋„๋ก ํ—ˆ๊ฐ€ํ•  ๋ฐฉ์•ˆ์— ๋Œ€ํ•˜์—ฌ ์กฐ์„ ์ด๋…๋ถ€์™€ ์ผ๋ณธ ์ •๋ถ€๊ฐ€ 1944๋…„ ๋ง์— ๋…ผ์˜ํ•œ ๋‚ด์šฉ์—์„œ๋„ ํ™•์ธ๋œ๋‹ค. ์กฐ์„ ์ด๋…๋ถ€๋Š” ๋‚ด์„ ๊ฒฐํ˜ผ ๊ฐ€์ •์˜ ์ „์ ์„ ์šฐ๋Œ€ํ•˜๋ ค ํ•˜๋ฉด์„œ๋„, ์œ„์žฅ๊ฒฐํ˜ผ์ด๋‚˜ ํƒˆ๋ฒ•ํ–‰์œ„๋ฅผ ์ œํ•œํ•˜๊ณ  ๋ฒ”์ฃ„๋ ฅ์ด๋‚˜ ์œ ์ „ ์งˆํ™˜์ด ์žˆ๋Š” ์ž๋Š” ํ†ตํ˜ผํ•  ์ˆ˜ ์—†๊ฒŒ ํ•˜๋Š” ๋ฐฉ์•ˆ๊นŒ์ง€ ๊ณ ๋ คํ•˜๋Š” ๋“ฑ ๋ชจ๋ฒ”์ ์ธ ๋‚ด์„ ๊ฒฐํ˜ผ๋งŒ ํฌ์„ญํ•˜๊ณ  ์‹ถ๋‹ค๋Š” ๋œป์„ ๋ณด์˜€๋‹ค. ์ด์— ๋น„ํ•ด ์ผ๋ณธ ์ •๋ถ€๋Š” ๊ธฐ์™•์˜ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ๋Š” ๊ทธ๋Œ€๋กœ ์ธ์ •ํ•˜๋˜, ํ†ตํ˜ผ ๊ฐ€์ •์„ ์šฐ๋Œ€ํ•˜์ง€ ์•Š์œผ๋ ค๋Š” ๋“ฑ ๋‚ด์„ ๊ฒฐํ˜ผ์„ ์žฅ๋ คํ•  ์ƒ๊ฐ์ด ์—†์Œ์„ ๋“œ๋Ÿฌ๋‚ด์—ˆ๋‹ค. ๊ฒฐ๊ตญ ์ผ์ œ์˜ ๋‚ด์„ ๊ฒฐํ˜ผ์— ๋Œ€ํ•œ ๋‚™๊ด€์  ์ธ์‹์€ ํ†ตํ˜ผ์˜ ํ™•์‚ฐ๊ณผ ๋ณธํ†  ์—ญ๋ฅ˜๋ฅผ ๊ณ„๊ธฐ๋กœ ๋ถ€์ •์ ์œผ๋กœ ์ „ํ™˜๋˜์—ˆ๊ณ , ์ƒ๋ฌผํ•™์  ์ธ์ข…์ฃผ์˜ ๋Œ€์‹  ๋ฏผ์กฑ ๋ฌธํ™”โ€ค๊ณ„์ธต์  ์ฐจ์ด๋ฅผ ๊ทผ๊ฑฐ๋กœ ํ†ตํ˜ผ๊ณผ ํ˜ผํ˜ˆ์ด๋ผ๋Š” ๊ถ๊ทน์  ๋™ํ™”๋ฅผ ๋ถ€์ •ํ•˜๊ธฐ์— ์ด๋ฅธ ๊ฒƒ์ด๋‹ค.ๅบ่ซ– 1. ๋ฌธ์ œ์ œ๊ธฐ์™€ ์—ฐ๊ตฌ ๋Œ€์ƒ 2. ์—ฐ๊ตฌ ๋™ํ–ฅ 3. ๋…ผ๋ฌธ์˜ ๊ตฌ์„ฑ๊ณผ ์ž๋ฃŒ ไธ€. 1910~30๋…„๋Œ€ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ์˜ ํ˜•์„ฑ ๋ฐ ์šด์šฉ 1. ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฐ ๋ฒ•์ œ์ƒ์˜ ๋ฏผ์กฑ ๊ตฌ๋ณ„ ๋ฌธ์ œ 1) ๋ณ‘ํ•ฉ ์ดํ›„ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฌธ์ œ์˜ ๋ฐœ์ƒ 2) ์กฐ์„ ์ด๋…๋ถ€์˜ ๋ฌธ์ œ ํ•ด๊ฒฐ ์‹œ๋„์™€ ํ•œ๊ณ„ 2. ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ์˜ ์„ฑ๋ฆฝ ๊ณผ์ • 1) ๊ณตํ†ต๋ฒ•์˜ ์ œ์ • ๋ฐ ๋ฏผ์กฑ ๊ตฌ๋ณ„ ์›์น™์˜ ๊ฒฐ์ • 2) ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ์˜ ์ •๋น„์™€ ์‹œํ–‰ 3. ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฒ•์ œ์— ์˜ํ•œ ํ˜ธ์  ์ด๋™ 1) ๆ—ฅๆœฌ็ฑ์—์„œ ๆœ้ฎฎ็ฑ์œผ๋กœ์˜ ์ด๋™ 2) ๆœ้ฎฎ็ฑ์—์„œ ๆ—ฅๆœฌ็ฑ์œผ๋กœ์˜ ์ด๋™ 3) ํ˜ธ์  ์ด๋™์ด ํ—ˆ๊ฐ€๋˜์ง€ ์•Š์€ ๊ด€๊ณ„ 4. ์†Œ๊ฒฐ ไบŒ. 1910~30๋…„๋Œ€ ๋‚ด์„ ๊ฒฐํ˜ผ์˜ ์„ ์ „ ๋ฐ ์‹คํƒœ 1. ์กฐ์„ ์ด๋…๋ถ€์˜ ๋‚ด์„ ๊ฒฐํ˜ผ ์„ ์ „๊ณผ ์กฐ์„ ์ธ์˜ ๋ฐ˜์‘ 1) ๋™ํ™”์ •์ฑ…์— ๋Œ€ํ•œ ๋…ผ๋ž€๊ณผ ๅ…ง้ฎฎ่žๅ’Œ์˜ ์ œ์ฐฝ 2) ์กฐ์„ ์ด๋…๋ถ€์˜ ๋‚ด์„ ๊ฒฐํ˜ผ ์žฅ๋ ค๋ก  3) ์กฐ์„ ์ธ ์‹์ž์ธต์˜ ๋‚ด์„ ๊ฒฐํ˜ผ ๋ฐ˜๋Œ€๋ก  2. ์กฐ์„ ์—์„œ์˜ ๋‚ด์„ ๊ฒฐํ˜ผ ์œ ํ˜•๊ณผ ์ถ”์ด 1) ์—ฐ๋„๋ณ„โ€ค์œ ํ˜•๋ณ„ ์ถ”์ด 2) ์ง€์—ญ๋ณ„โ€ค์ง์—…๋ณ„ ์ถ”์ด 3. ๋‚ด์„ ๊ฒฐํ˜ผ ๊ฐ€์ •์˜ ๊ฒฐํ˜ผ ๋™๊ธฐ์™€ ์ƒํ™œ์–‘์‹ 1) ์ƒ์ธต ๊ท€์กฑโ€ค๊ด€๋ฆฌ์™€ ์™•๊ณต์กฑ์˜ ์ •๋žต๊ฒฐํ˜ผ 2) ๊ฒฝ์ œ์  ์ดํ•ด๊ด€๊ณ„์˜ ํ•ฉ์น˜ 3) ์‹ ๋ถ„์‚ฌ๊ธฐ, ์„ฑ๋ฒ”์ฃ„, ๋™์ง€์  ๊ฒฐํ•ฉ 4. ๋‚ด์„ ์—ฐ์• โ€ง๋‚ด์„ ๊ฒฐํ˜ผ์œผ๋กœ ์ธํ•œ ์‚ฌํšŒ ๋ฌธ์ œ 1) ์—ฐ์• ์™€ ๊ฒฐํ˜ผ์˜ ๋ถˆ์—ฐ์† ๋ฐ ๋ณ€์‹ฌ 2) ไธ€ๅคซไธ€ๅฆป์˜ ๊ฐ€์กฑ์ œ๋„์™€์˜ ์ถฉ๋Œ 3) ๋ฏผ์กฑ ์ฐจ์ดยท๋ฏผ์กฑ ๊ฐ์ •์œผ๋กœ ์ธํ•œ ๊ฐˆ๋“ฑ 5. ์†Œ๊ฒฐ ไธ‰. ์ „์‹œ์ฒด์ œ๊ธฐ ๋‚ด์„ ๊ฒฐํ˜ผ ์ •์ฑ…๊ณผ ๋‚ด์„ ํ˜ผํ˜ˆ ๋ฌธ์ œ 1. ๅ…ง้ฎฎไธ€้ซ” ์ •์ฑ…์—์„œ์˜ ๋‚ด์„ ๊ฒฐํ˜ผ์˜ ์œ„์ƒ 1) ์กฐ์„ ์ด๋…๋ถ€์˜ ๋ชจ๋ฒ”์  ๋‚ด์„ ๊ฒฐํ˜ผ ์žฅ๋ ค 2) ์ผ๋ณธ ์ •๋ถ€์˜ ๋‚ด์„ ๊ฒฐํ˜ผยทํ˜ผํ˜ˆ ๋ฐ˜๋Œ€๋ก  ๋ฐฐ๊ฒฉ 2. ๋‚ด์„ ๊ฒฐํ˜ผยทํ˜ผํ˜ˆ ์—ฐ๊ตฌ์™€ ์ผ๋ณธ(์ธ)์˜ ็ด”ไธ€ๆ€ง ๋ฌธ์ œ 1) ๋‚ด์„ ํ˜ผํ˜ˆ์•„์˜ ์œ ์ „ ํ˜•์งˆ์— ๋Œ€ํ•œ ์šฐ์ƒํ•™์  ์—ฐ๊ตฌ 2) ๋‚ด์„ ์ผ์ฒด ์ •์ฑ…์˜ ์—ญ๋ฅ˜์™€ ์ผ๋ณธ(์ธ) ๋ณดํ˜ธ 3. ๊ณตํ†ต๋ฒ• ์ฒด์ œ์˜ ์žฌ๊ฒ€ํ† ์™€ ํ†ตํ˜ผ ์žฅ๋ ค์˜ ๋ฐฉ๊ธฐ 1) ํ˜ธ์ ์ƒ์˜ ๋ฏผ์กฑ ๊ตฌ๋ณ„ ์›์น™์˜ ๋…ผ๋ฆฌ์  ๋™์š” 2) ์กฐ์„ ์ด๋…๋ถ€์˜ ่ฝ‰็ฑๆกˆ๊ณผ ํ™ฉ๋ฏผํ™”์˜ ์กฐ๊ฑด 3) ๋‚ด๋ฌด์„ฑ์˜ ็งป็ฑๆกˆ๊ณผ ์ผ๋ณธ์ธํ™”์˜ ์กฐ๊ฑด 4. ์†Œ๊ฒฐ ็ต่ซ– ์ฐธ๊ณ ๋ฌธํ—Œ ๋ถ€๋ก Abstract ๆ—ฅๆ–‡ๆŠ„้Œ„Docto
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