黄芩汤对非酒精性脂肪肝大鼠肠道菌群的影响

Effects of Huangqin Decoction on gut microbiota in rats with nonalcoholic fatty liver disease

目的研究黄芩汤对非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)大鼠肠道菌群的影响。方法将大鼠随机分为空白组、模型组、阳性药(多烯磷脂胆碱,8 mg/kg)组及黄芩汤低、高剂量(5、20 g/kg)组,采用高脂饮食饲喂9周造模。ig给药5周后,采用全自动生化分析仪检测各组大鼠血脂和肝功能相关指标;采用HE染色法分析各组大鼠肝脏组织病理变化;采用16S rRNA测序技术分析各组大鼠肠道菌群变化。结果与模型组比较,黄芩汤低、高剂量组大鼠体质量明显降低(P<0.05、0.01),血脂指标总胆固醇(total cholesterol,TC)、三酰甘油(triacylglycerol,TG)、低密度脂蛋白胆固醇(lowdensitylipoproteincholesterol,LDL-C)和转氨酶指标丙氨酸氨基转移酶(alaninetransaminase,ALT)、天冬氨酸氨基转移酶(aspartate transaminase,AST)明显降低(P<0.01),血脂指标高密度脂蛋白胆固醇(high-density lipoproteincholesterol,HDL-C)明显升高(P<0.01),肝细胞脂肪变性与气球样变得到纠正,炎细胞浸润减少。16S rRNA测序结果显示,模型组大鼠肠道菌群较空白组发生变化;黄芩汤低、高剂量组大鼠肠道菌群较模型组sobs、heip和Shannon指数明显提升(P<0.05、0.01);在门和属水平上,黄芩汤高剂量组大鼠肠道菌群较模型组unclassified-f-Lachnospiraceae、布劳特氏菌属Blautia、Eubacterium coprostanoligenesgroup和瘤胃球菌属Ruminococcus丰度明显升高(P<0.05、0.01),放线菌门(Actinobacteria)、乳杆菌属Lactobacillus和双歧杆菌属Bifidobacterium丰度明显降低(P<0.05、0.01)。黄芩汤高剂量组较模型组明显上调京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)和直系同源簇(clusters of orthologous groups,COG)富集的功能水平(P<0.05、0.01)。结论黄芩汤可能通过改善NAFLD大鼠肠道菌群失调发挥对NAFLD的治疗作用。

Objective To investigate the effect of Huangqin Decoction(黄芩汤)on gut microbiota in rats with nonalcoholic fatty liver disease(NAFLD).Methods The rats were randomly divided into blank group,model group,positive drug group(polyene lecithin choline,8 mg/kg),low-dose(5 g/kg)and high-dose(20 g/kg)Huangqin Decoction group,and the rats were fed with high-fat diet for nine weeks to establish the NAFLD model.After five weeks of oral administration,the plasma lipids and liver function indexes were detected by fully automatic biochemical analyzer,the pathological changes of liver tissues were analyzed by HE staining and the changes of gut microbiota in rats were analyzed by 16 S rRNA sequencing.Results Compared with the model group,the weight of rats of low-dose and high-dose Huangqin Decoction group were significantly lower(P<0.05,0.01),the level of total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),alanine transaminase(ALT)and aspartate transaminase(AST)were significantly reduced(P<0.01),the level of HDL-C was elevated remarkably(P<0.01),the steatosis and ballooning degeneration of hepatocyte in liver tissues were corrected,and the inflammatory cell infiltration was decreased.16 S rRNA results showed that compared with the blank group,the gut microbiota in model group were changed;compared with the model group,the sobs,heip and Shannon indices of the gut microbiota in rats of low-dose and high-dose Huangqin Decoction group were significantly higher(P<0.05,0.01),the abundance of unclassified-f-Lachnospiraceae,Blautia,Eubacterium coprostanoligenes group and Ruminococcus in rats of highdose Huangqin Decoction group increased significantly(P<0.05,0.01),the abundance of Actinobacteria,Lactobacillus and Bifidobacterium in rats of high-dose Huangqin Decoction group decreased significantly(P<0.05,0.01).The functional level of Kyoto encyclopedia of genes and genomes(KEGG)and clusters of orthologous groups(COG)enrichment related to gut microbiota in rats of high-dose Huangqin Decoction group elevated significantly(P<0.05,0.01).Conclusion Huangqin Decoction might play a role in the treatment of NAFLD by regulating gut microbiota of rats with NAFLD.