Wnt/β-Catenin信号通路在非酒精性脂肪肝发病中的作用及阿托伐他汀的干预效果

Role and Intervention Effect of Atorvastatin Alleviating Liver Damage in Non-Alcoholic Fatty Liver Disease of Rats by Inhibiting the Activated Wnt / β-Catenin Singling Pathway

目的探讨大鼠非酒精性脂肪肝的发病机制及阿托伐他汀的干预改善作用。方法将60只清洁级SD大鼠随机分为正常对照组、非酒精性脂肪肝模型组和阿托伐他汀治疗高、中、低剂量组,各12只。高脂高糖饮食复制非酒精性脂肪肝模型,药物治疗组大鼠第12周开始接受阿托伐他汀灌胃治疗,模型组和正常对照组给予等剂量的溶剂羧甲基纤维素钠(CMC-Na)。分析各组大鼠血清天门冬酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)及超氧化物歧化酶(SOD)和丙二醛(MDA)水平,并检测基质金属蛋白酶(MMPs)和Wnt/β-Catenin通路蛋白的表达,HE染色分析肝脏组织病理变化。结果与正常对照组相比,高脂饮食模型组大鼠血清TG,TC,AST,ALT水平明显升高,羟脯氨酸含量增高,MMP2,MMP9,Wnt1,Wnt4,β-Caternin表达明显增强;而阿托伐他汀可显著改善上述异常,且具有剂量依赖性。结论阿托伐他汀能通过抑制Wnt/β-Catenin信号通路改善大鼠非酒精性脂肪肝肝脏损伤。

Objective To investigate the effect and mechanism of atovastatin on non-alcoholic fatty liver disease（NAFLD）.Methods60 clean SD rats were divided into 5 groups,control,NAFLD group and atovastatin groups at low /medium and high dose treatment,12 rats in each group.The NAFLD rats were duplicated by high glucose and fatty diets.The atorastatin group was giuen atovastatin gavage,and the control group and NAFLD group were given CMC-Na gavage with the same amount.The content of serum AST,ALT,TG,TC,SOD and MDA were assayed in each group.The expression of MMPs and Wnt/β-Catenin pathway members were detected by ELISA.The pathological changes of liver tissue were analyzed by HE staining.Results The results showed that the contents of AST,ALT,TG,TC,LDL were increased in NAFLD rats while the HDL concentration was decreased when compared with control.The results also revealed that MMP2,MMP9,Wntl,Wnt4 as well as β-Catenin was up-regulated dramatically when compared with the control group.Atovastatin treatment can relieve those aforementioned parameters dramatically with dosage dependence.Conclusion Activated Wnt/β-Catenin is participated in the pathogenesis of NAFLD and atovastatin exerts its effect mainly by inhibiting this pathway.