白藜芦醇对酒精依赖致大鼠肝损伤的相关研究

Protective effect of resveratrol on liver in alcohol dependent rats

目的观察白藜芦醇对酒精依赖大鼠肝损伤的保护作用。方法SD大鼠(Sprague-Dawley,SD)雄性随机数字表法分为空白对照组、酒精依赖模型组,选用20%酒精以及双瓶自由饮方式构造酒精依赖模型,模型制备成功将其随机分为酒精依赖模型组、白藜芦醇高、中、低剂量治疗组,每组8只。白藜芦醇治疗后提取大鼠肝脏组织,检测肝组织超氧化物歧化酶(SuperoxideDismutase,SOD)、谷胱甘肽过氧化物酶(Glutathione Peroxidase,GSH-PX)、过氧化氢酶(Catalase,CAT)和丙二醛(Malondialdehyde,MDA)水平,应用实时荧光定量聚合酶链反应(Real-time quantitative polymerase chain reaction,RT-qPCR)方法检测大鼠肝脏组织中腺苷酸活化蛋白激酶[Adenosine 5’-monophosphate(AMP)-activated protein kinase,AMPK]、过氧化物酶体增生物激活受体(Peroxisome proliferator-activated receptor alpha,PPARα)和过氧化物酶体增殖物激活受体γ辅激活因子1α(Peroxisome proliferator-activated receptor-γcoactivator 1 alpha,PGC1α)的基因表达水平。结果与空白组比,酒精依赖模型组大鼠肝组织SOD、GSH-PX与CAT均成下降趋势(P<0.05),酒精依赖模型组大鼠肝组织MDA明显增高(P<0.05);与酒精依赖模型组比,白藜芦醇高剂量和中剂量治疗组SOD、GSH-PX与CAT显著增高(P<0.05),MDA显著下降(P<0.05)。与空白组比较,酒精依赖模型组大鼠肝脏AMPKαmRNA、PPARαmRNA和PGC1αmRNA相对表达量显著降低,与酒精依赖模型组比,白藜芦醇高和中剂量组对AMPKαmRNA、PPARαmRNA和PGC1αmRNA的表达显著升高(P<0.05)。结论白藜芦醇可以有效改善酒精依赖大鼠肝脏组织氧化应激相关指标,其机制可能是白藜芦醇通过激活AMPK/PPARα/PGC1α信号通路降低肝脏组织氧化应激损伤进而对酒精依赖大鼠的肝脏发挥了保护作用。

Objective To observe the protective effect of resveratrol on liver injury in alcohol dependent rats.Methods SD male rats were randomly divided into control group and alcohol dependence model group.Alcohol dependence model was constructed by free drinking of 20%alcohol in two bottles.The model was successfully prepared and randomly divided into alcohol dependence model group,resveratrol high,medium and low dose treatment groups,with 8 rats in each group.After resveratrol treatment,the liver tissues of rats were extracted,and the levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),catalase(CAT)and malondialdehyde(MDA)expression in liver tissues were detected.The gene expression levels of adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK),peroxisome proliferator-activated receptor alpha(PPARα)and peroxisome proliferator-activated receptor-γcoactivator 1 alpha(PGC1α)in rat liver tissues were detected by qRT-PCR.Results Compared with the control group,SOD,GSH-PX and CAT in the liver tissue of the alcohol dependence model group showed a downward trend(P<0.05),and MDA in the liver tissue of the alcohol dependence model group was significantly increased(P<0.05).Compared with the alcohol dependence model group,SOD,GSH-PX and CAT in the high-dose and medium-dose resveratrol treatment groups were significantly increased(P<0.05),and MDA was significantly decreased(P<0.05).Compared with the control group,the relative mRNA expression of AMPKα,PPARαand PGC1αin the liver of rats in the alcohol dependence model group was significantly decreased.Compared with the alcohol dependence model group,the mRNA expression of AMPKα,PPARαand PGC1 in the high and middle dose groups of resveratrol was significantly increased(P<0.05).Conclusion Resveratrol can effectively improve the oxidative stress-related indicators in liver tissue of alcohol-dependent rats.The mechanism may be that resveratrol reduces oxidative stress injury in liver tissue by activating AMPK/PPARα/PGC1αsignaling pathway and thus protects the liver of alcohol-dependent rats.