复方茵丹汤调节肠道菌群改善急性肝内胆汁淤积OA
Compound Yindan Decoction Regulates Intestinal Microbiota to Ameliorate Acute Intrahepatic Cholestasis
目的 基于16S rRNA测序探讨复方茵丹汤对急性肝内胆汁淤积(AIC)大鼠肠道菌群结构及组成的影响.方法 40只SD大鼠随机分为正常组,模型组,复方茵丹汤(简称中药)高、中、低剂量组[24.48、12.24、6.12 g/(kg·d)],每组8只.除正常组外,其余各组于实验第3天灌胃α-萘异硫氰酸酯(AN IT,60 mg/kg)诱导AIC模型,各给药组于造模前后连续灌胃复方茵丹汤5天.采用16S rRNA测序分析肠道菌群.结果 α多样性分析显示,中药中、低剂量组物种多样性低于模型组(P<0.05).β多样性分析中,主坐标分析(PCoA)提示中药高、低剂量组物种组成差异明显;非加权配对算术平均法(UPGMA)聚类提示中药高剂量组菌群结构接近正常组;相似性分析(Anosim)与多响应置换过程(MRPP)分析显示中药高、低剂量组菌群结构差异显著(P<0.05).差异物种分析表明:与模型组比较,在门水平中药高剂量组拟杆菌门相对丰度升高,中药高、低剂量组厚壁菌门降低(P<0.01,P<0.05);在科水平中药高、低剂量组普雷沃菌科丰度升高(P<0.05),中药低剂量组乳杆菌科、毛螺旋菌科、颤螺旋菌科和瘤胃球菌科风度降低(P<0.01,P<0.05);在属水平中药高剂量组普雷沃菌相关菌属丰度升高(P<0.01),黏液乳杆菌属、瘤胃球菌属降低(P<0.05);中药低剂量组乳杆菌属、瘤胃球菌属等降低,普雷沃菌相关菌属升高(P<0.05).线性判别分析效应大小(LEfSe)分析提示,变形菌门、普雷沃菌科、变形菌纲在中药低剂量组特征明显,拟杆菌门、科、目在中药中剂量组特征明显.结论 复方茵丹汤可改善ANIT诱导的AIC大鼠胆汁淤积,其机制可能与调节肠道菌群结构(如拟杆菌门、厚壁菌门、普雷沃菌科等比例)、修复肠道屏障、减少内毒素及炎症因子释放有关.
Objective To investigate the effect of Compound Yindan Decoction(CYD)on the structure and composition of intestinal flora in rats with acute intrahepatic cholestasis(AIC)based on 16S rRNA sequencing.Methods Forty SD rats were randomly divided into normal group,model group,high,medium and low dose CYD(24.48,12.24,6.12 g·kg-1·d-1)groups,with 8 rats in each group.Except for the normal group,the other groups were given α-naphthylisothiocyanate(ANIT,60 mg/kg)to induce AIC model on the third day of the experiment,and each administration group was given CYD for 5 days before and after modeling.The intestinal flora was analyzed by 16S rRNA sequencing.Results The α diversity analysis showed that the species diversity of the middle and low dose CYD groups was lower than that of the model group(P<0.05).In the analysis of β diversity,principal coordinate analysis(PCoA)suggested that the species composition of the high and low dose CYD groups was significantly different;unweighted pair group method with arithmetic mean(UPGMA)clustering suggested that the flora structure of the high dose CYD group of was close to the normal group.Anosim and multirespons permutation procedure(MRPP)analysis showed that there was a significant difference in the structure of the flora between the high and low dose CYD groups(P<0.05).Differential species analysis showed that compared with the model group,the relative abundance of Bacteroidetes in the high dose CYD group increased at the phylum level,and the Firmicutes in the high and low dose CYD groups decreased(P<0.01,P<0.05).At the family level,the abundance of Prevotaceae in the high and low dose CYD groups increased(P<0.05),and the grace of Lactobacillaceae,Lachnospiraceae,Oscillospiraceae and Ruminococcaceae in the low dose CYD group decreased(P<0.01,P<0.05).At the genus level,the abundance of Prevotellaceae-related bacteria in the high dose CYD group increased(P<0.01),and the abundance of Lactobacillus and Ruminococcus decreased(P<0.05).In the low dose CYD group,Lactobacillus and Ruminococcus decreased,and Prevotellaceae-related bacteria increased(P<0.05).Linear discriminant analysis effect size(LEfSe)analysis showed that the characteristics of Proteobacteria,Prevotaceae and Proteobacteria were obvious in the low dose CYD group,and the characteristics of Bacteroidetes,families and orders were obvious in the middle dose CYD group.Conclusion CYD can improve ANIT-induced cholestasis in AIC rats,and its mechanism may be related to the regulation of intestinal flora structure(such as Bacteroidetes,Firmicutes,Prevotaceae,etc.),repair of intestinal barrier,and reduction of endotoxin and inflammatory factor release.
李晓玲;孙凤霞;张燕洁
首都医科大学附属北京中医医院肝病科(北京 100010)首都医科大学附属北京中医医院肝病科(北京 100010)首都医科大学附属北京中医医院肝病科(北京 100010)
复方茵丹汤急性肝内胆汁淤积大鼠肠道菌群中药复方
Compound Yindan Decoctionacute intrahepatic cholestasisratgut microbiotaChinese herbal compound
《中国中西医结合杂志》 2026 (5)
561-568,8
北京市自然科学基金青年项目(No.7244478)首都医科大学临床专科学院(系)培养基金开放课题(No.CCMU2022ZKYXZ008)
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