苓桂术甘汤对NASH大鼠肝组织DGAT2、PKCε的作用研究

Experimental study of Linggui Zhugan Decoction on DGAT2 and PKCε expression in NASH rats

[目的]探讨苓桂术甘汤对非酒精性脂肪性肝炎(NASH)大鼠肝组织DGAT2、PKCε的影响。[方法]高脂饮食饲养SD大鼠8周制备NASH模型,药物治疗4周后,自动生化分析仪检测血清肝功能(AST、ALT)、血脂(CHO、LDL、HDL、TG)水平,苏木精-伊红染色、油红O染色观察肝组织病理,RT-PCR检测DGAT2mRNA、PKCεmRNA,Western-blot检测DGAT2和PKCε蛋白的表达。[结果]苓桂术甘汤组、罗格列酮组能明显改善肝组织的脂肪变性和炎症程度,降低血清TG、ALT、AST,下调DGAT2、PKCεmRNA和蛋白的表达水平(P<0.05、P<0.01)。[结论]苓桂术甘汤可能是通过下调肝组织DGAT2、PKCεmRNA和蛋白的表达水平,对肝内脂质代谢和胰岛素抵抗起到了调节和改善作用,从而达到治疗NASH的目的,DGAT2/PKCε有可能成为治疗NASH的新靶点。

[Objective]To investigate the effect of Linggui Zhugan Decoction on DGAT2 and PKCεexpression in NASH rats.[Methods]High-fat diet was used to induce NASH model on SD rats for 8weeks.After 4weeks of treatment,the automatic biochemical analyzer was used to measure the serum liver function（AST,ALT）and blood lipid（CHO,LDL,HDL,TG）level.HE staining and oil-red O staining were used to observe the pathological changes of liver tissue.RT-PCR was used to detect the DGAT2 mRNA and PKCεmRNA.Western blot was used to observe the expression of DAGT2 and PKCεprotein.[Results]Linggui Zhugan Decoction and rosiglitazone can significantly improve the liver fatty degeneration and the degree of inflammation,reduce serum TG,ALT,AST,downregulate DGAT2,PKCεmRNA and protein expression levels（P0.05,P0.01）.[Conclusion]Linggui Zhugan Decoction may treat NASH through downregulation of hepatic DGAT2,PKCεmRNA and protein expression levels,thus adjusting the intrahepatic lipid metabolism and improving insulin resistance.DGAT2/PKCεmay become a new target for the treatment of NASH.