2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Chen, SH

Chen, SL

Chen, WM

Ma, XJ

Xu, HX

Yan, LP

2006-2007 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishedVoR allowe

PolyU Institutional Repository

 ????  ???????????????????CN 341206R, ISSN 10092501Email: ccpt96@ 21cn. comMay; 11( 5) : 574- 57720060324收稿  20060404修回香港赛马会慈善基金资助项目闫莉萍,女,博士生,研究方向:中药药理学?Tel: 13794483953  Email: lpyan@126. com马小军,通讯作者,男,博士生导师,研究方向:生药学?Tel: 01062819410  Email : xjma@ public. bta. net. cn葛根素对膳食诱导的高胆固醇血症大鼠的血脂调节作用闫莉萍1, 2 , 陈舜宏2, 3 ,陈伟民4 ,陈士林1, 2 , 马小军1 , 徐宏喜51中国协和医科大学,中国医学科学院药用植物研究所, 北京 100055;2深圳市中药药学及分子药理学研究重点实验室, 深圳 518057,广东;3深圳南粤药业有限公司,深圳 518055,广东;4香港理工大学应用生物与化学技术系, 香港; 5香港赛马会中药研究院,香港??  ??:观察葛根素对膳食诱导的高胆固醇血症大鼠的血脂调节作用,并对其机制进行探索???: SD大鼠随机分为 3组,正常组?模型组和葛根素组?模型组和葛根素组均给予富含胆固醇的饲料 4周,葛根素组每天灌喂葛根素溶液( 300 mgkg- 1d- 1 )?检测血清总胆固醇( TC)?甘油三酯 (TG)?高密度脂蛋白胆固醇(HDLc)和低密度脂蛋白胆固醇( LDLc)的含量?荧光定量 RTPCR分析羟基3甲基戊二酰CoA 还原酶 ( HMGR) , 羊毛固醇 14去甲基酶(CYP51) , 7羟化酶 ( CYP7A1)的 mRNA 转录水平???: 葛根素显著降低高胆固醇膳食引起的血清胆固醇的升高,降低动脉粥样硬化指数, 上调 CYP7A1的mRNA转录水平,对HMGR和 CYP51的转录水平没有影响???:这些数据表明葛根素能够降低血清胆固醇, 减低动脉粥样硬化发生危险?其降低胆固醇的作用可能是通过促进胆固醇转化为胆酸实现的????  高胆固醇血症; 血脂水平; 动脉粥样硬化;胆固醇平衡; 羟基3甲基戊二酰 CoA 还原酶;羊毛固醇 14去甲基酶; 7羟化酶?????: R965. 1?????: A? ? ? ?: 10092501( 2006) 05057404?????????????????????????????? [ 1] ?????????????????????????????????[ 2]????????????????????? ? ? ? ? ? ? ? ? ? ? ? ??? ? ?( C12H20C9) ????????????,????????????????????, ?????????????????????, ???????????????????, ??????????????????????????????????????????????????1  ?????1. 1  ??  SPF ????? SD??, 220~ 250 g,????????????????, ??????: 0016120?1. 2  ?????  ???????????; ???? ( TC)????? (TG)??????????(HDLc)?????????? ( LDLc)??????????????; Trizol?? Invitrogen; ?????SYBR green qPCR???????????;????PCR??ABI PRISM 7 000;??????? ALYCON?1. 3  ??????????[ 3]  SD ??, ???? 1??, ????,??????,?????????????????? 3?, ?? 8???????????(???14% ,?? 10% ,????? 76%) ;???????????? 2%????1%???5%??????;????????????( 300 mgkg- 1d- 1 )?1. 4  ????  4 ??, ????, ??????574?????????????? TC?TG?HDLc ?LDLc?1. 5  RTPCR????3????? CoA???(HMGR)????? 14???? ( CYP51)? 7??? ( CYP7A1) ? mRNA ????  ???????,?Trizol????? RNA?????? cDNA????? SYBR green RTPCR ????????? RTPCR?25 l???????? 2 l cDNA,50 nmolL- 1 ?? ( HMGR, ??: 5 CAACATCGTCACTGCCATC 3 , ??: 5 GATGCTCAAGCTGCCTTCT 3  ; CYP51, ? ?: 5  GATGCTCATCGGACTGCTG 3  , ? ?: 5  ATAAACGAAGCATAGTGGACC 3 ; CYP7A1, ??: 5 GGTTCTTCAGGTGTGAAACT 3  , ? ?: 5  CAGAGATCTTGCCTGGCTCT3 ; GAPDH, ??: 5 GTGGACCTCATGGCCTACAT 3 , ??: 5 TGTGAGGGAGATGCTCAGTG3 )??????????????: 95  , 30 s ???,???? 40 ???: 95  , 10 s ??; 60  ,30 s??; 72  , 30 s ???????? GAPDH ??? RNA ????????????? cDNA ???????????????????????????????? 3????1. 6  ?????  ???????  ???( x s)?????????????? NewmanKeul s???P< 0. 05?????????????????? GraphPad Prism 4. 02???2  ??2. 1  ???????????  ?? 1, 4??????,???? TC, TG, LDLc ?????????????????????, ????????????,?? HDLcLDLc ???????( P< 0. 05)?????????( 4. 1  0. 37 mmolL- 1 )????????? ?????? ( 3. 0 0. 17 mmolL- 1 )??( P< 0. 01)?????????,???? ( 3. 40  0. 28)??, ??????( 2. 50  0. 20)??????????????( P< 0. 01)?? 1 ??? 300 mgkg- 1d- 1?? 4 ???????????( x  s, mmolL- 1 , n= 8) ?? ???? ???? ????????? ???????????? 2. 1 0. 03 0. 79  0. 26 0. 47 0. 06 1. 32  0. 07??? 4. 0 0. 38 0. 92  0. 18 2. 43 0. 33 1. 23  0. 09???? 2. 9 0. 19c 0. 84  0. 08 1. 82 0. 24 1. 20  0. 05与模型组比较c P< 0. 012. 2  ?????????????????  ???????????????????? HMGR?CYP51?????????????? CYP7A1?????????????,HMGR? CYP51 ?????????? ( P < 0. 01, ? 1)???CYP7A1, ????????????( P< 0. 05) ,????????????????(?1)?? 1 ??? 300 mgkg- 1d- 1?? 4 ??????????????? HMGR( A)?CYP51(B)? CYP7A1( C) mRNA???????( x  s, n= 8)与正常对照组比较bP < 0. 05, cP < 0. 01;与模型组相比较eP < 0. 05;HMGR:羟基3甲基戊二酰CoA还原酶; CYP51:羊毛固醇 14去甲基酶; CYP7A1: 7羟化酶575??????????? 2006May; 11( 5)3  ???????, ???????????????,?????????????????????( 2%) ,??( 0. 5% )????( 5% )?????????????????????,????????????? [ 3] ??????????????????????????, ?????????????? [ 4] ??????, ???????????????: ?????????????,??????????????????????, ?????????? [ 5] ???,??????,????????( TCHDLc)????, ????????????????????????????????????, ???????????????????????, ?????????????, ????????????????????????????????,????????????????,??????????????????????????????????????????,???????????????????????????? 3 ???: ( 1)????????; ( 2)????????; ( 3)???????????????????????????, ??????????????? HMGR? CYP51 ?????????,?????????????????????????????? CYP7A1????????, CYP7A1????????????????? [ 6] ,??????????????, ???????(??)???? 50% [ 7]???, ??????????????????????????,??????????????????????,????? CYP7A1 ????????????????????[ 8]???,??????,???????????????,?????????,??????????????????????????????????????????????????????????????????? ? ? ?1 Ross R. The pathogenesis of atherosclerosis: a perspective forthe 1900s[ J] . Nature, 1993; 362: 801- 92 Prasad K, Kalra J. Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E [ J] . Am Heart J,1993; 125: 958- 733 Nakamura H, Izumiyama N, Nakamura K, Ohtsubo K. Ageassociated ultrastructural changes in the aortic intima of rats withdietinduced Hypercholesterolemia [ J] . Atherosclerosis, 1989;79: 101- 114  Chiang MT, Chen YC, Huang AL. Plasma lipoprotein cholesterol levels in rats fed a diet enriched in cholesterol and cholicacid[ J] . Int J Vitam Nutr Res, 1998; 68: 328- 345 Hoekstra M, Out R, Kruijt JK , Van Eck M, Van Berkel TJ.Diet induced regulation of genes involved in cholesterol metabolism in rat liver parenchymal and Kupffer cells[ J] . J Hepatology, 2005; 42: 2400- 76 Russell DW, Setchell KDR. Bile acid biosynthesis[ J] . Biochemistry , 1992; 31: 4737- 497 Yang TTC, Koo MWL. Chinese green tea lowers cholesterol level through an increase in fecal lipid excretion[ J] . Life Sci,2000; 66: 411- 238 Kawakami Y , Tsurugasaki W, Yoshida Y , Igarashi Y, Nakamura S, Osada K. Regulative actions of dietary soy isoflavoneon biological antioxidative system and lipid metabolism in rats[ J] . J Agric Food Chem, 2004; 52: 1764- 8Regulatory effect of puerarin on lipid profile in hypercholesterolemic ratsYAN Liping1, 2 , CHEN Shunhong2, 3, CHEN Weimin4 , CHEN Shilin 1, 2, MA Xiaojun1, XU Hongxi51Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100055 , China;2State Key Laboratory ofChinese Medicine and Molecular Pharmacology , Shenzhen 518057 , Guangdong , China;3Shenzhen South China Pharmaceutical Co. Ltd. , Shenzhen 518055, Guangdong , China;4Department of Applied Biology and Chemical Technology ,the Hong Kong Polytechnic University , Hong Kong SAR , China ;5Hong Kong Jockey Club Institute of Chinese Medicine,Hong Kong SAR , ChinaABSTRACT  AIM: To investigate the regulatory effectof puerarin on lipid profile in dietinduced hypercholesterolemic rats and elucidate the mechanisms involved.METHODS: SD rats were randomly divided into the576 Chin J Clin Pharmacol Ther 2006 May; 11( 5)control group, hypercholesterolemia group and puerarintreated group. The hypercholesterolemia group and puerarintreated group were given diet rich in cholesterol. Inthe meant ime, the puerarintreated group was orally administrated with puerarin ( 300 mgkg- 1d- 1 ) . The lipidprofile was investigated by the content of serum TC, TG,HDLc and LDLc. The mRNA levels of 7hydroxylase( CYP7A1) , 3hydroxy3methylglutarylCoA reductase(HMGR) and lanosterol 14demethylase ( CYP51) wereanalyzed by real time RTPCR. RESULTS: Puerarinmarkedly attenuated the increased serum total cholesterolinduced by hypercholesterolemic diet . It caused a significant reduction in the atherogenic index. Expression ofmRNA of CYP7A1 was signif icantly enhanced but not forthose of HMGR and CYP51. CONCLUSION: These data indicate that puerarin can reduce the atherogenic properties of dietary cholesterol in rats. Its hypocholesterolemic funct ion may be due to promoting the conversion ofcholesterol into bile acids.KEY WORDS  hypercholesterolemia; serum lipids levels; atherosclerosis; 3hydroxy3methylglutarylCoA reductase; lanosterol 14demethylase; 7hydroxylase577??????????? 2006May; 11( 5)

Regulatory effect of puerarin on lipid profile in hypercholesterolemic rats

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