当飞利肝宁胶囊改善高脂饮食联合四氯化碳诱导的大鼠非酒精性脂肪性肝炎的作用机制

Mechanism of Dangfei Liganning Capsule attenuating nonalcoholic steatotic hepatitis induced by high-fat diet combined with carbon tetrachloride in rats

目的研究当飞利肝宁胶囊对高脂饮食联合四氯化碳(CCl4)诱导的大鼠非酒精性脂肪性肝炎(NASH)防治作用及机制。方法雄性Wistar大鼠,随机分为正常对照组、NASH模型组和当飞利肝宁胶囊治疗组。正常组大鼠喂食普通饲料,模型和治疗组给予高脂饲料,治疗组同时每天予当飞利肝宁胶囊灌胃干预。8周后,除正常组外,其余大鼠腹腔注射CCl4,48 h后处死并收集血清和肝脏组织。观察肝脏组织病理学改变,检测血清ALT、AST、乳酸脱氢酶(LDH)、总胆红素(TBil)、胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和游离脂肪酸(FFA)水平,检测血清空腹血糖(FBG)、空腹胰岛素(FIN)并计算HOMA指数,以及血清脂联素和肝组织肿瘤坏死因子(TNFα)含量。结果肝组织油红O染色显示,模型组出现大面积小叶内肝细胞脂肪变性,HE染色同时显示出肝细胞气球样变性和炎性细胞浸润,而治疗组肝细胞脂肪变性、气球样变和炎性浸润明显减轻。模型组血清ALT、AST、LDH、TG、LDL、FFA水平较正常组显著升高(P<0.05),HOMA指数和肝组织TNFα含量也显著升高(P<0.05),血清脂联素含量明显下降;治疗组大鼠上述指标均显著改善(P<0.05)。结论当飞利肝宁胶囊对高脂饮食联合CCl4诱导的大鼠NASH具有显著防治作用,对脂联素、TNFα表达水平的调节和改善胰岛素抵抗是其重要机制。

Objective To study the therapeutic effect and potential mechanism of Dangfei Liganning Capsules on nonalcoholic steatotic hepatitis（NASH） induced by high-fat diet and carbon tetrachloride in rats.Methods Male Wistar rats were randomly divided into normal group,model group and treatment group.The rats of normal group were fed with a standard diet,while the rats of model and treatment groups were fed with high-fat diet.In addition the rats of treatment group were gastrically perfused with Dangfei Liganning Capsules everyday.Rats from model and treatment groups were intraperitoneally injected with CCl_4 48 h before being sacrificed.The pathology of liver and ALT,AST,LDH,TBIL,TC,TG,HDL,LDL,FFA in serum were tested.The fasting blood glucose（FBG） and fasting insulin（FIN） were tested to calculate HOMA index.Serum adiponectin and hepatic levels of TNF α were assessed.Results Compared with normal group,model group showed massive steatosis with Oil Red-O stain in liver lobules with hepatocyte ballooning and inflammatory infiltration with H-E stain appeared in centrilobules,which were all improved in the treatment group.Levels of serum ALT,AST,LDH,TG,LDL and FFA increased dramatically in model rats,HOMA index and TNF α content in liver tissue also elevated.Serum adiponectin decreased dramatically（P〈0.05）.The above examined indexes in treatment group were improved obviously（P〈0.05）.Conclusion Dangfei Liganning Capsules could alleviate high fat-diet combined with toxin induced NASH in rats,and the regulation of adiponectin and TNF α level,as well as attenuating insulin resistance contribute to the underlying mechanism.