摘要
目的 :观察吡格列酮对小鼠胆盐肠肝循环转运相关基因的表达影响。方法 :将16只小鼠随机分为两组:对照组(normal control,NC)、药物组(medicine,M),分别给予普通饮食、普通饮食加吡格列酮(pioglitazone)灌胃,喂养10周后处死小鼠取血、胆汁、小鼠肝脏、小肠组织,生化分析仪分析小鼠血样代谢指标,q RT-PCR技术检测各组小鼠组织内胆盐肠肝循环相关基因的表达。结果:M组小鼠胆汁中胆盐含量NC组显著升高,肝脏法尼醇X受体(farnesoid X receptor,FXR)及胆盐合成相关基因胆固醇7羟化酶(cytochrome P450 enzyme7 A1,CYP7A1)、胆固醇27羟化酶(CYP7A1cytochrome P450 enzyme27 A1,CYP27A1)以及胆盐转运基因胆盐输出泵基因(bile salt export pump,BSEP)、牛黄胆酸钠转运基因(sodium/taurocholate cotransporting polypeptide,NTCP)的表达较NC组也明显升高(P<0.01)。肝脏组织免疫组化证实了M组BSEP在蛋白层面表达升高。M组小肠组织内胆盐转运基因顶膜钠离子依赖性胆汁酸转运体(apical sodium dependent bile acid transporter,ASBT)的表达较NC组明显升高(P<0.01)。结论 :吡格列酮能够诱导胆盐合成相关基因的表达,并上调胆盐在肝脏以及小肠内的转运相关基因的表达,在转录水平参与胆盐肠肝循环的调控。
Objective： To investigate the effect of Pioglitazone on genes invol ved in bile acid enterohepatic circulation in C57bl mice.Methods： C57bl mice were randomly divided into two groups,named NC（normal control,n=8） group and M（medicine,n=8）group,respectively.Mice in NC group were fed with chow diet,while mice in M group were fed with both Pioglitazone and chow diet,and the feeding last for 10 weeks.At the end of our experiment,all mice were sacrificed and blood samples,liver and intestine tissues were collected.Fully automatic biochemical analyzer was used for the detection of blood metabolic parameters,and q RT-PCR was used for the detection of gene expression,which were involved in bile acid enterohepatic circulation.Results： Mice in group M displayed an increased biliary BA content.FXR,CYP7 A1 and CYP27A1,which play important roles in bile acid synthesis were detected in an induced expression in group M mice.Hepatic bile acid transporters BSEP and NTCP were also detected in an increased expression in group M compared with group NC.Immunohistochemical examination testified an increased protein expression of BSEP in mice liver tissue.ASBT,a gene regulates intestinal bile acid reabsorption,were detected in an increased expression in group M mice.Conclusion： Pioglitazone increased the expression of genes involved in bile acid synthesis,bile acid transport,as well as intestinal reabsorption,which indicates the drug,may play a great role in regulating genes involved in enterohepatic circulation.
出处
《南京医科大学学报（自然科学版）》
CSCD
北大核心
2017年第12期1562-1566,共5页
Journal of Nanjing Medical University(Natural Sciences)
基金
国家自然科学基金面上项目(81470881)
