天然产物研究与开发 ›› 2018, Vol. 30 ›› Issue (7): 1143-1148.doi: 10.16333/j.1001-6880.2018.7.008

• 研究论文 • 上一篇    下一篇

基于胆汁酸代谢网络分析绞股蓝总皂苷降脂作用的机制

鲁艳柳1,2,杜艺玫1,2,秦琳1,2,马菲菲1,2,凌蕾1,2,吴迪1,2,周旭美1*,何芋岐1,2*   

  1. 1遵义医学院药学院药学实验室,遵义 563009;2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 563003
  • 出版日期:2018-08-08 发布日期:2018-08-08
  • 基金资助:

    国家自然科学基金(81402985,81660685,81560673);教育部春晖计划(Z2016003);贵州省科技重大专项(黔科合重大专项字[2015]6010);贵州省科学技术基金项目(黔科合JZ字[2015]2010号,黔科合J字[2015]2158号);贵州省教育厅自然科学研究项目(黔教合KY字[2015]373号);贵州省留学人员科技创新项目(黔人项目资助合同(2015)03号);遵义医学院优秀青年人才项目(15zy-004);上海市复方中药重点实验室开放基金(14DZ2271000)

Hypolipemic Mechanism of Saponins from Gynostemma Pentaphylla Based on Analysis of Bile Acids

LU Yan-liu1,2,DU Yi-mei1,2,QIN Lin1,2,MA Fei-fei1,2,LING Lei1,2,YANG Tao1,2,LU An-jing1,2,WU Di1,2,ZHOU Xu-mei1*,HE Yu-qi1,2*   

  1. 1The Pharmaceutical Lab,School of Pharmacy,Zunyi Medical University,Zunyi 563099,China; 2Key Laboratory of Basic Pharmacalogy of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi 563003,China
  • Online:2018-08-08 Published:2018-08-08

摘要: 绞股蓝总皂苷具有显著的降低血脂的作用,然而其机制尚未明确。课题组在前期研究的基础上,将33只C57BL/6J雄性小鼠随机分为3组,对照组(ND组)、模型组(HFD组)和绞股蓝皂苷组(HFD+GP组),分别给予维持饲料和高脂饲料,从16周开始,每日分别灌胃给予绞股蓝总皂250 mg/kg和等体积的空白溶剂,至38周,收集小鼠的血清和肝脏样本。通过HE染色观察肝脏组织的病理变化,检测血清总胆固醇和低密度脂蛋白水平,利用UPLC-MS/MS技术对小鼠肝脏14种胆汁酸含量进行分析,采用实时荧光定量PCR检测Cyp7a1、Cyp8b1、Fxr、Shp、Lrh1、Hnf4α基因表达水平。与对照组比较,模型组有明显的脂肪泡结构,给予绞股蓝总皂苷可以明显减轻肝脏组织的病理改变。与模型组比较,绞股蓝总皂苷可以显著降低血清中TC和LDL-C含量,显著降低肝脏中牛磺熊去氧胆酸(TUDCA)、甘氨鹅去氧胆酸(GCDCA)和甘氨脱氧胆酸(GDCA)含量,显著升高肝脏中鹅去氧胆酸(CDCA)、脱氧胆酸(DCA)和牛磺脱氧胆酸(TDCA)含量,并在上调肝脏Cyp7a1、Cyp8b1、FxrLrh1基因表达的同时下调Shp的基因表达。绞股蓝总皂苷降脂作用的潜在靶点可能与FXR介导的胆汁酸代谢通路有关,为进一步深入探讨绞股蓝总皂苷降脂作用及其机制提供了参考。

关键词: 绞股蓝总皂苷, 胆汁酸代谢网络, 高脂血症

Abstract: The saponins from Gynostemma Pentaphylla have significant effects on reducing blood lipid,however,the mechanism is not clear.The C57BL/6J male mice were randomly divided into three groups,including normal diet group (ND),high fat diet group (HFD),and gypenosides group (HFD+GP).Mice in HFD and HFD+GP group were fed with high fat diet for 38 weeks,and treated with 0.1% CMC-Na and gypenosides (250 mg/kg) respectively,from 16 weeks to 38 weeks.In ND group,mice were fed with normal diet for 38 weeks.At the end point,serum and liver tissue were collected.Mice livers were observed by HE staining.Serum TC and LDL-C levels were measured by commercially available kit.Bile acid metabolic profile was quantified by UPLC-MS/MS.Quantitative real-time-PCR was applied to analyze mRNA expression levels of Cyp7a1,Cyp8b1,Fxr,Shp,Lrh1 and Hnf4α genes.Gypenosides significantly decreased serum TC and LDL-C levels.The hepatic levels of tauroursodeoxycholic acid (TUDCA),glycochenodeoxycholic acid (GCDCA),and glycodesoxycholic acid (GDCA) were decreased,but those of chenodeoxycholic acid (CDCA),deoxycholic acid (DCA),and taurodeoxycholic acid (TDCA) were increased.The gene expression levels of Cyp7a1,Cyp8b1,Fxr and Lrh1 were up-regulated by gypenosides.However,the level of Shp was down-regulated.The potential therapeutic targets of gypenosides may be genes involved in bile acids regulation.

Key words: gypenosides, bile acid metabolic profile, hyperlipidemia

中图分类号: 

R285.5