复方降脂3号对高胆固醇血症新西兰白兔胆固醇-胆汁酸代谢的影响  

Effects of Fufang Jiangzhi No.3 on cholesterol-bile acid metabolism in rabbits with hypercholesterolemia

作　　者：毛奇琦[1] 孙旭[1] 邱冬妮[1] 傅晓东[2] 刘懿[1] 王文健[2] 

机构地区：[1]复旦大学华山医院消化科,上海200040 [2]复旦大学华山医院中医科,上海200040

出　　处：《中西医结合学报》2010年第5期453-457,共5页Journal of Chinese Integrative Medicine

摘　　要：目的:探讨复方降脂3号对胆固醇-胆汁酸代谢的影响。方法:24只新西兰白兔分为正常对照组、模型组和复方降脂3号组,每组8只。模型组和复方降脂3号组予高胆固醇饮食诱导高血脂,并给予相应药物灌胃。治疗4周后,检测白兔外周血清总胆固醇、胆汁酸水平,酶联免疫吸附测定法检测肝脏胆固醇7α-羟化酶(cholesterol 7α-hydroxylase,CYP7A1)活性,实时荧光定量聚合酶链式反应法检测CYP7A1、法尼酯X受体(farnesoid X receptor,FXR)靶基因胆盐输出泵(bile saltexport pump,BSEP)和短异源二聚体伴侣(small heterodimer partner,SHP)受体mRNA表达情况。结果:模型组胆固醇和胆汁酸水平较正常对照组明显升高(P<0.01);肝脏CYP7A1活性降低,mRNA表达下降(P<0.01);BSEP和SHP mRNA表达明显增加(P<0.01)。与模型组比较,复方降脂3号组胆固醇水平明显下降(P<0.01);肝脏CYP7A1活性升高,mRNA表达增加(P<0.01);BSEP和SHP mRNA表达明显下降(P<0.01)。复方降脂3号组胆汁酸含量与模型组比较,差异无统计学意义。结论:复方降脂3号可能通过上调CYP7A1表达和抑制BSEP、SHP mRNA表达,促进肝脏内胆固醇合成胆汁酸,继而降低血清胆固醇水平。Objective：To investigate the effects of Fufang Jiangzhi No.3,a compound traditional Chinese herbal medicine,on cholesterol-bile acid metabolism in rabbits with hypercholesterolemia and to explore the mechanism. Methods：Twenty-four male New Zealand white rabbits were randomly assigned into normal control group, untreated group and Fufang Jiangzhi No.3 group,with 8 rabbits in each group.Rabbits in the untreated group and Fufang Jiangzhi No.3 group were fed high cholesterol diet to induce hypercholesterolemia.After 4-week treatment,serum total cholesterol and bile acid contents were assessed.Activity of cholesterol 7α-hydroxylase （CYP7A1） in liver tissues was measured by enzyme-linked immunosorbent assay.The expressions of CYP7A1,bile salt export pump（BSEP） and small heterodimer partner（SHP） mRNAs in liver tissues were observed by real-time fluorescent quantitative polymerase chain reaction. Results：Compared with the normal control group,serum total cholesterol and bile acid contents in the untreated group were increased（P〈0.01）.Activity of CYP7A1 and expression of CYP7A1 mRNA were decreased and expressions of BSEP and SHP mRNAs were increased in liver tissues in the untreated group as compared with the normal control group（P〈0.01）.Serum total cholesterol level,and expressions of BSEP and SHP mRNAs in the Fufang Jiangzhi No.3 group were lower than those in the untreated group（P〈0.01）. The CYP7A1 activity and expression of CYP7A1 mRNA in the Fufang Jiangzhi No.3 group were increased as compared with the untreated group（P〈0.01）,however,there was no significant difference in bile acid between the Fufang Jiangzhi No.3 group and the untreated group. Conclusion：Fufang Jiangzhi No.3 can up-regulate the expression of CYP7A1 mRNA,raise the activity of CYP7A1,and inhibit the expressions of BSEP and SHP mRNAs to regulate the metabolism of total cholesterol in rabbits.

关 键 词：胆汁酸 胆固醇 方剂 法尼酯X受体 胆固醇7Α-羟化酶 胆盐输出泵 短异源二聚体伴侣受体 兔 

分 类 号：R285.5[医药卫生—中药学]