膈下逐瘀汤对非酒精性脂肪性肝炎大鼠肝脏脂肪酸代谢酶的影响

目的:观察膈下逐瘀汤对非酒精性脂肪性肝炎(NASH)大鼠肝脏脂肪酸代谢酶的影响,探讨膈下逐瘀汤防治NASH的作用机制。方法:30只SD雄性大鼠随机分为正常组、模型组、膈下逐瘀汤组,每组10只,正常组予标准饲料喂养,其他两组予高脂饲料喂养,同时膈下逐瘀汤组予14g/(kg.d)的膈下逐瘀汤流浸膏灌胃,正常组和模型组以等容量的蒸馏水灌胃,连续12周。HE染色后光镜下观察肝脏组织病理学改变;生化法测定肝组织匀浆TG、CHOL含量;ELISA法检测血清游离脂肪酸(FAA)和肝组织脂肪酸合酶(FAS)、乙酰CoA羧化酶(ACC)、肉毒碱棕榈酸转移酶-1(CPT-1)、硬脂酰辅酶A去饱和酶-1(SCD-1)含量。结果:模型组大鼠肝组织出现重度脂肪变,肝细胞气球样变,肝小叶出现不同程度的炎细胞浸润和点片状坏死灶;肝脏NAFLD活动度积分(NAS)较正常组明显增高(P0.01),血清FAA和肝组织TG、CHOL含量较正常组明显增高(P0.01);肝组织ACC、FAS表达较正常组显著升高(P0.01),而CPT-1、SCD-1蛋白表达则较正常组明显下降(P0.01)。应用膈下逐瘀汤干预后,大鼠肝组织NAS较模型组明显下降(P0.05);血清FAA、肝组织TG、CHOL水平及ACC、FAS表达均较模型组显著下降(P0.01,P0.05);而肝组织CPT-1和SCD-1表达则较模型组明显升高(P0.01,P0.05)。结论:高脂饮食诱导的NASH大鼠存在着脂肪酸代谢紊乱;膈下逐瘀汤能一定程度纠正肝组织脂肪酸代谢酶的紊乱,减少脂肪酸对肝脏损伤有关,这可能是其防治NASH的作用机制之一。

Effect of Gexia Zhuyu Decoction on Fatty Acid Metabolic Associated Enzymes in Liver of Rats with Nonalcohlic Steatohepatitis

Objective:To observe the effect of Gexia Zhuyu Decoction on fatty acid metabolism associated enzymes in liver of rats with nonalcohlic steatohepatitis(NASH),and to explore the mechanism of preventing NASH with Gexia Zhuyu Decoction.Methods:30 male rats were randomly and respectively divided into the normal group,the model group and the Gexia Zhuyu Decoction group.The rats in the normal group were fed with satandard fodder mixtures,the others with high-fat diet.Meanwhile,the rats in the Gexia Zhuyu Decoction group were fed with Gexia Zhuyu Decoction liquid extract by daily gavage at the dose of 14g/(kg·d),the rats in the normal and model groups were fed with isometrical distilled water by daily gavage.At the end of 12th week,all the rats were put to death.The liver pathological changes were evaluated under light microscope after HE staining,the contents of liver homogenate TG and CHOL were detected with biochemistry assay,the contents of serum free fatty acid(FFA),liver fatty acid synthase(FAS),acetyl CoA carboxylase(ACC),carnitine palmitoyl trans-ferase(CPT) and Stearoyl CoA desat urease(SCD) were measured with ELISA.Results:In this model,the hepatic tissue showed serious fatty change,ballooning degeneration of hepatocytes,with varying degrees of inflammatory cell infiltration and spotty and patchy necrosis inhepatic lobules.The NAFLD activity sore was higher than that in the normal group(P<0.01).The amounts of serum FFA,liver homogenate TG and CHOL were enhanced than those in the normal group(P<0.01).The contents of liver ACC,FAS were higher(P<0.01),but the levels of CPT-1,SCD-1 proteins were lower than those in the normal group.With the treatment of Gexia Zhuyu Decoction,the NAS of rats liver were obviously decreased than that in the model group.The contents of serum FFA,liver TG,CHOL and the expressions of ACC,FAS were obviously decreased than those in the model(P<0.01,P<0.05),but the expressions of CPT-1and SCD-1 proteins were obviously increased than those in the model(P<0.01,P<0.05).Conclusions:There is a disorder of fatty acid metabolism in NASH rats induced by high-fat diet,to some degree,Gexia Zhuyu Decoction can correct the disorder of fatty acid metabolic associated enzymes and relieve the injury of fatty acid,which is probably the important mechanism of prevention and treatment from NASH.