中药组分HJJB方对小鼠非酒精性脂肪性肝炎的防治作用及其对肠道菌群的影响

Preventive and therapeutic effects of HJJB Formula on non-alcoholic steatohepatitis in mice and its influence on intestinal bacteria

目的:探讨HJJB方治疗小鼠非酒精性脂肪性肝炎(NASH)的作用及其对肠道菌群的影响。方法:36只C57BL/6小鼠随机分为正常组、模型组、HJJB方组和奥贝胆酸组,每组9只,采用高脂饮食诱导的NASH小鼠模型,第11周开始各药物组小鼠灌胃给予相应药物,持续4周,观察指标如下:(1)肝组织HE染色和非酒精性脂肪肝活动评分(NAS);(2)肝组织甘油三酯(TG)含量和血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性;(3)血清TG、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)含量;(4)血清空腹血糖(FINS)、空腹胰岛素(FBG)含量和稳态模型胰岛素指数(HOMA-IR);(5)肠道菌群多样性分析(16S rRNA测序分析)。结果:与正常组比较,模型组小鼠的肝组织出现明显的脂肪变性和散在的炎细胞浸润,肝组织TG含量和NAS评分,血清ALT和AST活性,TG、TC、LDL-C、FINS、FBG水平及HOMA-IR显著升高(P<0.01),肠道拟杆菌门(Bacteroidetes)的丰度显著降低(P<0.05)、厚壁菌门(Firmicutes)的丰度显著升高(P<0.05)。与模型组比较,HJJB方组和奥贝胆酸组上述肝组织病理变化显著减轻,肝组织TG含量和血清ALT、AST、TC、LDL-C、FINS、FBG水平及HOMA-IR显著降低(P<0.05,P<0.01),且HJJB方能纠正上述高脂饮食诱导的肠道菌群紊乱。结论:HJJB方具有良好的治疗NASH小鼠的作用,并能有效纠正肠道菌群紊乱、维持肠道菌群稳态。

Objective:To investigate the effect of HJJB Formula on non-alcoholic steatohepatitis(NASH)in mice and its intervention on intestinal bacteria.Methods:Thirty-six C57BL/6 mice were randomly divided into normal group,model group,HJJB Formula group and oberlic acid group,with 9 mice in each group.NASH mice model induced by high-fat diet was adopted.Type I,the mice in each drug group were given corresponding drugs by gavage from the 11th week,and lasted for 4 weeks.The observation indexes were as follows:(1)HE staining and NAS score of liver tissue;(2)liver Tissue triglyceride(TG)content and serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities;(3)serum TG,total cholesterol(TC),low density lipoprotein cholesterol(LDL-C)content;(4)serum fasting blood glucose(FINS),fasting insulin(FBG)and HOMA-IR;(5)analysis of intestinal flora diversity(16S rRNA sequencing analysis).Results:Compared with the normal mice,the liver tissue of the model mice showed obvious fatty degeneration and scattered inflammatory cell infiltration.The TG content and NAS score of liver tissue,serum ALT and AST activities,TG,TC,LDL-C,FINS,FBG levels and HOMA-IR increased significantly(P<0.01),and the abundance of intestinal Bacteroidetes decreased significantly(P<0.05),the abundance of Firmicutes increased significantly(P<0.05).Compared with the model mice,the pathological changes of liver tissue in HJJB Formula group and Oberlic acid group were significantly reduced,and the TG content of liver tissue,serum levels of ALT,AST,TC,LDL-C,FINS,FBG and HOMAIR were significantly reduced(P<0.05,P<0.01),and HJJB Formula group could correct the intestinal bacteria disorder induced by high-fat diet.Conclusion:HJJB Formula has fine therapeutic effect on NASH mice,and can effectively correct the intestinal bacteria disorder and maintain the intestinal bacteria homeostasis.