实用医学杂志 ›› 2023, Vol. 39 ›› Issue (10): 1232-1236.doi: 10.3969/j.issn.1006⁃5725.2023.10.007

• 基础研究 • 上一篇    下一篇

肝内胆汁淤积对小鼠回盲部胆汁酸谱及肠道菌群的影响 

雷榆1 胡亚欣2 余蕾3 程明亮2 程卓4 丛硕2 蒲茜3 郑林5    

  1. 贵州医科大学1 药学院5 贵州省药物制剂重点实验室药用植物功效与利用国家重点实验室(贵阳550004); 2 贵州医科大学附属医院(贵阳550004);3 贵阳市妇幼保健院(贵阳550004);4 北京大学第三医院(北京 100083) 
  • 出版日期:2023-05-25 发布日期:2023-05-25
  • 通讯作者: 郑林 E⁃mail:1037930332@qq.com
  • 基金资助:
    贵州省中医药管理局项目(编号:QZYY⁃2018⁃016)

Effect of intrahepatic cholestasis on bile acid spectrum and intestinal flora in ileocecum of mice 

LEI Yu, HU Yaxin,YU Lei,CHENG Mingliang,CHENG Zhuo,CONG Shuo,PU Qian,ZHENG Lin.   

  1. School of Pharma⁃ ceutical Sciences,Guizhou Medical University,Guiyang 550004,China
  • Online:2023-05-25 Published:2023-05-25
  • Contact: ZHENG Lin E⁃mail:1037930332@qq.com

摘要:

目的 研究肝内胆汁淤积对肠道内胆汁酸代谢谱和肠道菌群的影响,为进一步揭示肝内 胆汁淤积对机体的影响极其机制研究做铺垫。方法 将 20 只雄性 BALB/C 小鼠均分为正常组和模型 组,基于多反应监测技术(MRM)方法的靶向代谢组学,分析肝内胆汁淤积对于小鼠肠道内 33 种胆汁酸 的影响;高通量测序技术检测小鼠回肠和结肠内肠道菌群的变化。结果 两组在胆汁酸谱的分布上有着 很大的差异,初级胆汁酸 CA、熊去氧胆酸(ursodeoxycholic acid,UDCA)、牛黄胆酸(taurocholic acid,TCA) 等在模型组组富集,而猪脱氧胆酸(hyodeoxycholic acid,HDCA)、甘氨石胆酸(glycocholic acid,GLCA)、 牛磺猪去氧胆酸(taurodeoxycholic acid,THDCA)、牛磺石胆酸(taurolithocholic acid,TLCA)等次级胆汁酸 在正常组富集,差异有统计学意义。与正常组相比,模型组的结肠菌群丰度和多样性均显著降低,而回 肠段的菌群丰度和多样性显著升高。两组间菌群差异明显,在正常组罗斯拜瑞士氏菌、Butyricicoccus、 Mucispirillum 等益生菌占优势,而模型组嗜胆盐菌、红椿菌占优势。结论 肝内胆汁淤积对小鼠回盲 部胆汁酸谱产生影响,HDCA、GLCA 等次级胆汁酸显著减少,可能与肠屏障功能减弱以及肠道菌群变化有关。 

关键词: 肝内胆汁淤积, 胆汁酸谱, 靶向代谢组学, 肠道菌群

Abstract:

Objective To study the effects of intrahepatic cholestasis on intestinal bile acid metabolism and intestinal flora,and to lay the groundwork for further revealing the effect of intrahepatic cholestasis on the body and its mechanism. Methods Twenty male BALB/C mice were divided into model group and normal group,with 10 mice in each group. Based on multiple reaction monitoring(MRM)⁃based targeted metabolomics,the effect of intrahepatic cholestasis on 33 bile acids in the intestines of mice was analyzed,and the changes of intestinal flora in ileum and colon were detected by high ⁃throughput sequencing. Results There was a great difference in the distribution of bile acid spectrum between the two groups. Primary bile acids such as CA,UDCA and TCA were enriched in the model group,while secondary bile acids such as HDCA,GLCA,THDCA and TLCA were enriched in the normal group. The difference was statistically significant. Compared with those in the normal group,the abundance and diversity of colonic flora in the model group were significantly decreased,while those in the ileal segment were significantly increased. There were significant differences in flora between the two groups. In the normal group,probiotics such as Roseberg,Butyricicoccus,Mucispirillum and other probiotics were dominant,while cholhalophilic bacteria and Toona sinensis were dominant in the model group. Conclusion Intrahepatic cholestasis has an effect on bile acid spectrum of ileocecum in mice,and the secondary bile acids such as HDCA and GLCA are significantly decreased,which may be related to the weakening of intestinal barrier function and the changes of intestinal flora. 

Key words: intrahepatic cholestasis, bile acid spectrum, targeted metabolomics, intestinal flora