临床儿科杂志 ›› 2021, Vol. 39 ›› Issue (7): 520-.doi: 10.3969/j.issn.1000-3606.2021.07.010

• 实验研究 • 上一篇    下一篇

敲除巨噬细胞对胆管结扎小鼠胆汁淤积的干预作用

田心蓓, 陈珊珊, 王伟鹏, 吴博, 朱景, 周莹, 肖永陶   

  1. 上海交通大学医学院附属新华医院 上海市儿科医学研究所 上海市小儿消化与营养 重点实验室(上海 200092)
  • 发布日期:2021-07-01
  • 通讯作者: 周莹,肖永陶 电子信箱:zhouying 01 @xinhuamed.com.cn, xiaoyongtao@xinhuamed.com.cn
  • 基金资助:
    国家自然科学基金(No. 81974058)

Effect of macrophage knockout on cholestasis in mice with bile duct ligation

TIAN Xinbei, CHEN Shanshan, WANG Weipeng, WU Bo, ZHU Jing, ZHOU Ying, XIAO Yongtao   

  1. Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Pediatric Research, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
  • Published:2021-07-01

摘要: 目的 探讨巨噬细胞对胆汁酸代谢的影响。方法 以结扎7周龄雄性CD11b-DTR小鼠胆总管方法建立胆 汁淤积模型,2周后测定肝脏及结肠内容物中胆汁酸谱及肠道菌群组成。将28只小鼠分为假手术(Sham)组、假手术干 预(DT)组、胆管结扎(BDL)组、胆管结扎干预(BDL+DT)组。结果 与Sham组相比,BDL组肝脏中初级胆汁酸及总胆 汁酸含量均显著增加,BDL+DT组肝脏中非结合初级胆汁酸及总胆汁酸含量则较BDL组明显减少,差异有统计学意义 (P均<0.05)。在结肠内容物中,BDL+DT组较BDL组结合初级胆汁酸含量降低,差异有统计学意义(P< 0 . 05)。与Sham组相比,BDL组肠道 Prevotella的属水平相对丰度增加,而BDL+DT组Escherichia、Clostridium和Segmented filamentous bacteria(SFB)较BDL 组属水平相对丰度增加,差异均有统计学意义(P均

关键词: 巨噬细胞; 胆汁酸; 肠道菌群; 胆道闭锁; 小鼠

Abstract: Objective To explore the effect of macrophages on bile acid metabolism. Methods The cholestasis model was established by ligating the common bile duct of 7 -week-old male CD 11 b-DTR mice. After 2 weeks, the bile acid profile and intestinal flora composition in the liver and colon were measured. Twenty-eight mice were divided into four groups: sham group, sham intervention (DT) group, bile duct ligation (BDL) group and bile duct ligation intervention (BDL+DT) group. Results Compared with the sham group, the contents of primary bile acid and total bile acid in the liver of the BDL group were significantly increased, while the contents of unbound primary bile acid and total bile acid in the liver of the BDL+DT group were significantly decreased compared with the BDL group, and the differences were statistically significant (all P< 0 . 05 ). In colonic contents, BDL+DT group had lower level of binding primary bile acid than that of the BDL group, and the difference was statistically significant (P< 0 . 05 ). The expression level of cyp 7 a 1 , a key enzyme for bile acid synthesis, in the BDL+DT group was lower than that in the BDL group, and the difference was statistically significant (P< 0 . 05 ). Conclusion Conditional macrophage knockout can interfere with cholestasis by changing the structure of intestinal microbiota.

Key words: macrophages; bile acid; intestinal microbiota; biliary atresia; mouse