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Effects of Ecdysterone on the Expression of Tumor Necrosis Factorα and Nuclear Factor κ B in Nonalcoholic Fatty Liver Disease of Rats

摘要:目的: 研究蜕皮甾酮对非酒精性脂肪性肝病大鼠模型肿瘤坏死因子α(TNFα)与核因子κB(NFκB)表达的影响，并探索其可能的作用机制。 方法 :健康成年SD大鼠36只,随机分为正常对照组12只与实验组24只;正常对照组喂以普通基础饲料,实验组应用高脂饲料喂养。实验12周末时将造模成功的实验组大鼠随机分为模型组与蜕皮甾酮治疗组2个亚组,每组12只;正常对照组喂以普通基础饲料至16周,模型组继续应用改良高脂饲料喂养至16周,蜕皮甾酮治疗组大鼠在高脂饮食同时加用蜕皮甾酮灌胃。实验16周末时处死3组所有大鼠;检测肝脏指数,血清与肝组织生化指标及肝组织病理改变;ELISA法检测肝脏TNFα水平;免疫组化检测各组大鼠肝组织中核因子κB蛋白表达情况。 结果 :蜕皮甾酮治疗组血清胆固醇(TC)、丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)明显低于模型组(212±058比263±024,Plt;005;5336±1848比8460±3627,P＜005;14020±3595比24359±3638,P＜001);蜕皮甾酮治疗组与模型组相比肝组织丙二醛(MDA)水平降低明显(18454±1645比23928±2376,P＜001),超氧化物歧化酶(SOD)活力增加显著(942±052比518±043,P＜001),肝脏指数显著降低(435±037比504±046,P＜001)，肝组织脂肪变性程度和炎症活动度明显减轻(546±037比630±049,P＜001)。蜕皮甾酮治疗组与模型组相比TNFα与核因子κB水平明显减轻(4304±748比6156±727,2465±539比4504±746,P值均＜001)。 结论 :蜕皮甾酮具有改善高脂饮食诱发的非酒精性脂肪性肝病大鼠肝脏酶学功能,通过增加肝组织SOD的含量和减少MDA的含量来减轻肝组织氧化应激水平,减轻肝组织TNFα和核因子κB来减轻肝脏炎症,发挥防治非酒精性脂肪性肝病的作用。Abstract: Objective: To investigate the effect and possible mechanism of ecdysterone on the expression of tumor necrosis factoralpha (TNFα) and nuclear factor κ B (NFκB) in rats with nonalcoholic fatty liver disease of rats. Methods : A total of 36 male Sprague Dawley rats were randomly divided into two groups, who were fed with highfat diet (experimental group, n=24) and normal basic food (normal control, n=12) respectively. At the end of the 12th week, the experimental group was randomly divided into two subgroups: model group and ecdysterone group, each group contained 12 rats. From the 13th week, the rats in the normal control group and model group were lavaged with normal sodium, and the rats in the ecdysterone group were lavaged with ecdysterone at 10 mg·kg-1·d-1. At the end of the 16th week, all rats were weighed, narcotized, sacrificed, and the liver index, biochemical indicators in serum and liver tissues and the hepatic pathological changes were observed. The expression of TNFα was detected by ELISA and the expression of NFκB was measured by immunohistochemical staining. Results : At the end 16th week in ecdysterone group, the serum levels of cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reduced markedly (212±058 vs 263±024 and 5336±1848 vs 8460±3627, both P＜005; 14020±3595 vs 24359±3638, P＜001); the tissue content of malondialdehyde (MDA) was decreased evidently (18454±1645 vs 23928±2376, P＜001), while the activity of superoxide dismutase (SOD) was enhanced notably (942±052 vs 518±043, P＜001); the liver index was decreased significantly in comparison with that inmodel group (435±037 vs 504±046, P＜001); the degree of fatty degeneration and inflammation were relieved dramatically (546±037 vs 630±049, P＜001). The expression of TNFα and the levels of NFκB were significantly lower (4304±748 vs 6156±727 and 2465±539 vs 4504±746, both P＜001) in ecdysterone group compared with model group. Conclusion : The effects of ecdysterone in preventing NAFLD in rats could be related to the increase of SOD content in hepatic tissue and the decrease of MDA content, tumor necrosis factorα and NFκB.