维生素E与熊去氧胆酸对非酒精性脂肪肝大鼠的协同肝保护机制

Synergistic Protective Mechanism of Vitamin E and Ursodeoxycholic Acid on Nonalcoholic Fatty Liver in Rats

非酒精性脂肪性肝病(NAFLD)是全世界最常见的肝病,而非酒精性脂肪肝炎(NASH)是其中一种,具有潜在的严重性,其发展涉及多次打击过程。一些临床研究表明,熊去氧胆酸(UDCA)和维生素E单独或联用对治疗NASH患者有明显的改善作用,但效果具有一定可逆性。而关于UDCA和维生素E联用治疗NASH的机制研究也尚少,因此本研究希望通过探究UDCA与维生素E联用对改善NASH大鼠的效果与机制,为NASH的治疗提供更多的理论依据。构建NASH大鼠模型,通过喂养不同饮食分别设立对照组,模型组和2组给药治疗组(UDCA单独用药;UDCA/VitE联合用药),12周后对大鼠肝组织进行病理分析,检测AST、ALT、MDA、SOD等生化指标和组织NF-κB、TNF-α蛋白表达水平,对比不同组间差异,评估给药治疗的疗效,分析可能的机制;UDCA能有效改善NASH的各种组织特征或生化指标,并且与维生素E一起对NASH大鼠的肝保护具有协同作用,这种协同作用可能与抑制肝细胞脂肪变性和炎细胞浸润,减轻肝损伤和胰岛素抵抗有关。

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease in the world,and non-alcoholic steatohepatitis(NASH) is one of them,with potential severity,and its development involves multiple strikes.Some clinical studies have shown that ursodeoxycholic acid(UDCA) and vitamin E(VitE) alone or in combination have a significant improvement in the treatment of NASH patients,but the effect is reversible.There are few studies on the mechanism of UDCA combined with vitamin E in the treatment of NASH.Therefore,this study hopes to provide more theoretical basis for the treatment of NASH by exploring the effect and mechanism of UDCA combined with vitamin E on improving NASH rats.A rat model of NASH was established.The control group,model group and two treatment groups(UDCA alone;UDCA/VitE combination) were established by feeding different diets.After 12 weeks,the liver tissue of the rats was pathologically analyzed AST,ALT,MDA,SOD and tissue NF-κB,TNF-α protein expression levels were measured,the differences between groups were compared.With these results,the efficacy of therapy was evaluated,and the possible mechanisms were analyzed.UDCA can effectively improve various tissue characteristics or biochemical indicators of NASH,with VitE.UDCA/VitE combination have a synergistic effect on liver protection in NASH rats.This synergistic effect may be related to inhibition of hepatic steatosis and inflammatory cell infiltration,and reduction of liver damage and insulin resistance.