非诺贝特对胆汁酸代谢通路的作用机制研究

发布时间：2018-04-11 12:20

本文选题：非诺贝特 + 胆汁酸　；参考：《中国新药杂志》2017年19期

【摘要】：目的:研究非诺贝特对小鼠肝脏及肠道胆汁酸调控途径的作用机制。方法:C57/BL小鼠随机分为正常对照组(ND组)、模型组(HFD组)和非诺贝特给药组(HFD/FF组)。模型组及非诺贝特给药组持续给予高脂饲料。高脂饲料给予16周后,给药组给予非诺贝特35 mg·kg~(-1)。对照组持续给予普通饲料。给药时间22周。取肝脏组织HE染色,测定血糖、血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、谷丙转氨酶(ALT/GPT)及谷草转氨酶(AST/GOT)水平,检测肝脏或肠组织中Cyp7a1,Cyp8b1,FXR,SHP,Lrh1,Hnf4α,Fgf15,Fgfr4,JNK1/2和ERK1/2的基因表达,LC-MS分析肝脏中胆汁酸的含量。结果:非诺贝特对血糖、TC和LDL-C等指标有显著改善作用。非诺贝特显著回调Cyp7a1的表达。同时非诺贝特对肝脏FXR,肠道Fgf15等也有显著回调作用。非诺贝特引起肝脏去氧胆酸(DCA)异常升高。结论:非诺贝特可能通过上调Cyp7a1,加快胆固醇代谢,进而降低体内胆固醇水平,并进一步对血糖调节产生影响。过量的DCA产生可能是非诺贝特引起肝损伤的一种重要机制。
[Abstract]:Aim: to study the mechanism of fenofibrate on the regulation of bile acids in the liver and intestine of mice.Methods: C57 / BL mice were randomly divided into two groups: normal control group (ND group), model group (HFD group) and fenofibrate administration group (HFD-rFF group).The model group and fenofibrate group were continuously given high fat diet.After 16 weeks of high fat diet, fenofibrate was given 35 mg / kg of fenofibrate.The control group was given general diet continuously.The administration time was 22 weeks.Results: fenofibrate significantly improved blood glucose TC and LDL-C.Fenofibrate significantly callback the expression of Cyp7a1.At the same time, fenofibrate also has a significant effect on liver FXR, intestinal Fgf15 and so on.Fenofibrate caused abnormal elevation of hepatic deoxycholic acid (DCA).Conclusion: fenofibrate may increase cholesterol metabolism by up-regulating Cyp7a1, and then decrease cholesterol level and further influence the regulation of blood glucose.Excessive production of DCA may be an important mechanism of fenofibrate induced liver injury.
【作者单位】：遵义医学院国家级药学实验教学示范中心药学实验室;遵义医学院基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室;遵义医学院附属医院药剂科;
【基金】：国家自然科学基金资助项资助项目(81402985,81560673,81660685) 贵州省科技重大专项资助项目(黔科合重大专项字[2015]6010) 贵州省科学技术基金资助项目(黔科合J字[2015]2158号,黔科合JZ字[2015]2010号) 贵州省出国留学人员择优资助计划(黔人项目资助合同(2015)03号) 上海市复方中药重点实验室开放基金资助项目(14DZ2271000) 国家级/省级大学生创新创业项目(201510661002)
【分类号】：R965

【相似文献】