Studies on the effects of CCl₄on exocrine pancreas

의학과/석사[한글] 약물은 주로 간장 smooth surfaced endoplasmic reticulum에 존재하는 효소에 의하여 대사되므로 약물의 작용기간이나 작용강도는 대략 이 효소의 대사속도에 따라 결정된다. phenobarbital의 반복 투여는 약물대사 효소를 증가 시킬 뿐 아니라 외분비 기능도 증가시킨다. 담취외분비 기능에 있어서는 phenobarbital 반복투여로 담취액 분비량 및 bilirubin 배출을 증가시키며 amylase, lipase 활성을 현저히 증가시키나 cholate 농도는 감소시킨다고 보고되고 있다. 사염화탄소를 동물에 투여하면 간장 endoplasmic reticulum에 조직학적 변화를 일으키고 microsome 효소작용이 감소되며 간장 단백합성도 저하시킨다. 본 실험에 있어서는 이러한 약물대사효소 항진인자인 phenobarbital과 효소억제 물질인 CC/4를 투여하여 간 및 취외분비선에 미치는 영향을 비교 검토하였다. 본 실험에서 얻어진 결과를 요약해 보면 다음과 같다. 1. 사염화탄소 단독투여군의 치사율은 34%이나 phenobarbital 전처치후 사염화탄소 투여군에서는 치사율이 15%로 감소되었다. 2. phenobarbital 투여군에서는 담취액 분비량의 현저한 증가를 사염화탄소 투여군에서는 현저한 감소를 나타냈다. 3. 담취액 bilirubin 농도는 phenobarbital 단독 투여군에서는 감소를 사염화탄소 단독투여군에는 증가를 보였으며, phenobarbital 전처치후 사염화탄소 투여로 bilirubin 배출량과 농도가 현저히 증가되었다. 4. cholate 농도와 배출량은 대조군에 비해 모든 실험군에서 현저히 감소하였다. 5. 당취액 lipase 치는 phenobarbital 투여군과 phenobarbital 전처치후 사염화탄소 투여군에서 증가를 보였으나 사염화탄소 단독투여군에서는 별 변동을 볼 수 없었다. 6. 담취액 amylase치는 phenobarbital 단독투여군에서는 현저한 증가를, 사염화탄소 단독 투여군에서는 감소를 phenobarbital 전처치 후 사염화탄소 투여군에서는 경도의 증가를 보였다. 위의 사실들로 보아 사염화탄소 투여로 인한 간손상으로 간외분비 뿐 아니라 취외분비기능도 저하되나 phenobarbital 전처치로 사염화탄소의 간취독성이 강약 됨을 알 수 있다. [영문] The metabolism of many drugs and also of steroid hormones is mediated by enzymes located in the microsomal fraction in smooth surfaced endoplasmic reticulum of mammalian liver. The duration and intensity of action of many drugs are largely determined by the speed at which they are metabolized in the body. Repeated administration of phenobarbital results in the induction of enzymes that metabolize a number of drugs. Lee et al. reported that daily administration of phenobarbital in rats significantly increased the activities of amylase and lipase in the pancreatobiliary juice, but the concentration of cholate in the bile was significantly lower in the treated group than that in the control group. After animals were treated with CCl^^4, histological changes were shown in the endoplasmic reticulum, decreased microsomal enzyme activity and decreased hepatic protein synthesis were apparent. The purpose of the present report was to study the interaction between a "microsomal-stimulating" agent such as phenobarbital and a "microsomal-depressing" agent such as CCl^^4 on hepatic and pancreatic functions in rats. The results obtained are summarized as follows: 1. The mortality rate of Ccl^^4 treated group was 34% and was decreased this figure to 15% with phenobarbital pretreatment. 2. In animals treated with phenobarbital the volume of biliary-pancreatic secretion was markedly elevated but the volume was decreased significantly in animals treated with CCl^^4. 3. Total bilirubin output was elevated markedly in the CCl^^4. treated group of rats pretreated with phenobarbital. The bilirubin concentration was increased in CCl^^4 treated group and decreased in the group treated with phenobarbital alone. 4. The concentration and tal output of cholate in the bile were significantly lower in the all experimental group than control group. 5. In the animals treated with phenobarbital alone and phenobarbital plus CCl^^4, the activity of lipase in pancreatobiliary juice was elevated, while in the animals treated with CCl^^4 alone no change was observed. 6. The activity of amylase in the pancreatobiliary juice was decreased in the CCl^^4 treated group, but elevated markedly in phenobarbital group and also elevated in phenobarbital CCl^^4 group. By the above results, it is concluded when the liver was damaged by CCl^^4, the exocrine function of pancreas and liver was decreased simultaneously. However, in the animals pretreated with phenebarbital, the toxicity of CCl^^4 on the liver and pancreas was reduced.restrictio

지속분비 자극이 취효소 배출에 미치는 영향

의학과/박사[영문] [한글] 취장 외분비는 secretin으로 분비 촉진이, pancreozymin 및 미주신경 자극으로 효소 분 비촉진이 유발된다. 취 효소단백은 endoplasmic reticulum의 ribosome에서 합성되어 강내로 이동하고 smoot h surfaced vacuole을 거쳐 완전한 zymogen granule을 형성하여 저장되었다가 분비 자극 으로 세포외로 배출된다고 생각되어 왔다. 요사이는 효소단백 배출이 zymogen granule에 서 뿐만 아니라 cytoplasm에서도 일어나며 이는 기능적으로 서로 다른 pool이 있기 때문 이라고 생각한다(Rothman and Isenman, 1974). Liebow와 Rothman(1975)은 3H-chymotrypsinogen의 장내 주입으로 수분후에 취액에서 3H -Chymotrypsinogen을 발견할 수 있어 분비된 취효소의 일부가 장에서 흡수되어 다시 취장 을 통해 분비되는 소화효소의 장취 순환이 이루어질 것이라고 주장하였다. 이상의 견해를 더 추구하고져 체중 27g 내외의 토끼를 사용하여 취외분비 변동 및 정맥 내 취액 재투여로 인한 영향을 검색하였다. 체중 kg당 매시간 secretin lu와 CCK-PZ 2u 또는 acetylcholine 0.3mg을 정맥내 주입하였으며 취관에는 polyethylenetube를 삽입하며 20분 간격으로 취액을 받았다. 취액 재주입군은 1회 채취액을 5회 채취때, 2회 채처액은 6회때 등으로 각각 정맥내 주입하였다. 실험 종료후 취장을 적출하여 조직내 효소활성을 측정하였다. 실험 결과를 요약하면 다음과 같다. 1. Secretin과 pancreozymin을 계속 정맥내 주입하므로 취액분비는 높은 치를 유지 하 나 취단백 및 취효소치는 조기상승 후 계속적인 자극에도 불구하고 시간 경과에 따라 철 저히 저하 되었다. 2. Secretin과 acetylcholine의 계속 정맥내 주입 실험에서도 취액분비는 지속적인 높 은 치를 보이나 취단백 및 효소분비는 조기 증가 반응 후 시간 경과에 따라 현저히 저하 되었다. 3. 취효소 분비가 저하된 시기에 다른 분비 자극 pancreozymin주입 자극예에서는 acetr lcholine, acetylcholine 주입시엔 pancreozymin을 주면 취효소 분비 증가를 나타내었다. 4. 취액을 정맥내 투여한 실험예의 효소분비치는 취액을 투여 않은 예보다 증가하였다. 5. 취조직내 효소량은 secretin과 acetylcholine 자극으로 감소를 나타냈으나 secretin 과 pancreozymin 자극예 에서는 오히려 약간 증가하였다. 그러나 정맥내 취액 주입으로는 별변동이 없었다. 이상의 실헙성적을 종합해 보면 취효소 단백의 일부는 혈행에서 취선포를 통하여 장내 로 재분비 되는 장취순환을 한다고 생각되며 pancreozymin 자극 또는 acetylcholine 자극 으로 분비되는 서로 다른 취효소 fool이 취선포내에 있는지는 더욱 추구해 볼 과제로 생 각된다. Effect of continuous stimulation on the pancreatic enzyme secretion Young Sook Pae, M.D. Department of Medical Science The Graduate School, Yonsei University (Directed by Professor Sa Suk Hong, M.D) Two hypotheses are suggested as secretory mechanism of digestive enzymes from exocrine pancreas. One of them is classical Palade's packaging-exocytosis theory, in which the enzymes synthetized in the ribosomal complex are packaged into zymogen granules and migrates to the apex of the cell where its contents are secreted by stimulation. Alternate hypothesis, i.e. equilibrium theory. was recently proposed by Rothman and his co-workers. In this model digestive enzymes move bidirectionally through specialized membranes, so that enzyme in various compartment can be in "equilibrium" with each other. The cytoplasm acts as rapidly equilibrating pool (REP) and zymogen granule as slowly equilibrating pool (SEP). Recently Rothman and his co-workers suggested that at least some digestive enzymes undergoes an enteropancreatic circulation, similar to the enterohepatic circulation of bile salt : that is, intact digestive enzyme molecules are absorbed by the intestine and circulated by way of the blood stream to acinar cell. Finally the enzyme molecules are secreted back into the intestine. Present study was undertaken to investigate the changes of secretory functions by continuous stimulation and the intravenous homologous enzymes could he resecreted via the pancreas in rabbits. The albino rabbits of broth sexes weighing 2.0-2.5kg were used and anesthetized with secobarbital(30mg/kg). After catheterization into femoral vein and pancreatic duct of the rabbit, secretin (1u/kg/hr) with either cholecystokinin-pancreozymin (CCK - PZ,2u/kg/hr)or acetylcholine (0.3mg/kg/hr) was infused Constantly (12ml/kg/hr) by Harvard infusion pump. The pancreatic juice was collected every 20 minutes, and protein and amylase activity were determined by spectrophotometrically at 280 nm and by Sumner method, respectively. In the experiment of re-infusion of pancreatic juice the first juice was injected at the time of 5th collection and the Second juice at 6th collection, and so on The results obtained are summarized as fellows. 1. The flow rate of the pancreatic secretion was relatively constant by continuous infusion of secretin with either pancreozymin or acetylcholine. 2. Both proteins and amylase contents were increased markedly and then progressively defreaaed by continuous stimulation with pancreozymin or acetylcholine in animals under secretin infusion and at the end of 4 hour-infusion the enzyme proteins were reduced nearly to the level of saline control. 3. At the end of 4 hour-infusion, when the protein enzyme levels were decreased markedly. alternative secretory stimulus, i,e. pancreozymin in acetylcholine infusion or acetylcholine in pan creozymin infusion, increased significantly the protein and amylase secretion. 4. After intravenous injections of own pancreatic juice, the pancreatic protein and amylase levels were showed relative increases and consequently the decreasing levels of both the protein and amylase were over riden. Nevertheless, flow rates of pancreatic juice were not changed. 7. The enzyme contents of pancreatic tissue after 4 hour-stimulation were decreased in concomittant secretin-acetylcholine stimulation but not changed in secretin-pancreosymin stimulation. By these findings it is conceived teat at least some digestive enzymes can be resecreted via pancreas from blood stream to intestine and it should further investigated Whether the acetylcholine-responding or pancreozymin-responding pools are present in the pancreas.restrictio