鹅去氧胆酸对大鼠肠道菌群结构及肠道功能的影响

Effects of Chenodeoxycholic Acid on the Rat Intestinal Microbiota Structure and Gut Functions

为探究胆汁酸对动物肠道菌群组成的影响,明确胆汁酸、肠道细菌与肠道功能间的关系,通过胆总管结扎,构建肠道内源胆汁酸缺乏的大鼠模型,模型大鼠灌服鹅去氧胆酸7 d后,取结肠组织,分别进行HE染色、ELISA和Western Blot杂交试验,观察肠道组织形态变化,探究鹅去氧胆酸对大鼠肠道炎症因子和NF-κBp50/p65表达水平的影响;利用高通量测序分析大鼠肠道菌群结构的变化,揭示鹅去氧胆酸影响肠道菌群结构和肠道功能的机制。结果表明,鹅去氧胆酸能够显著降低肠道中芽孢梭杆菌属、红椿菌属及丹毒菌属细菌的丰度,改变大鼠肠道菌群结构,下调p50、p65亚基的表达水平,抑制NF-κB信号通路,降低TNF-α、IL-6、IL-1β等炎症因子的表达水平,有益于维持肠道正常功能。综上所述,胆汁酸可能通过改变肠道菌群结构,影响肠道功能。本试验为胆汁酸及肠道菌群的重要生理功能的研究提供了理论依据。

To explore effect of chenodeoxycholic acid on rat intestinal microbiota structure and clarify the relations of chenodeoxycholic acid,intestinal microbiota and gut functions,intestinal cholic acid lacking rat model was established by bile duct ligation,the model rats were gavaged with cholic acid for 7 days with collecting the colon tissue and extracting total protein. Intestinal morphology was observed by HE staining. ELISA and Western Blot were performed to determine the expression levels of inflammatory factors and NF-κBp50/p65. High-throughput sequencing was performed to analyze the change of intestinal microbiota structure. These studies were conducted to reveal the mechanism by which chenodeoxycholic acid affects intestinal microbiota and intestinal functions. The results showed chenodeoxycholic acid significantly reduced the quantities of Clostridiaceae,Coriobacteriaceae and Erysipelotrichaceae,down-regulated the expression levels of NF-κB p50/p65,repressed the NF-κB pathway,and attenuate the expression level of inflammatory factors such as TNF-α,IL-6 and IL-1β,which were beneficial to the normal functions of the rat gut. In conclusion,chenodeoxycholic acid could change the intestinal microbiota structure and affect gut functions.This study will supply a theoretical basis for revealing the more important physiological functions of cholic acid and intestinal microbiota.