摘要:目的: 研究蛻皮甾酮對(duì)非酒精性脂肪性肝病大鼠模型腫瘤壞死因子α(TNFα)與核因子κB(NFκB)表達(dá)的影響,并探索其可能的作用機(jī)制。 方法 :健康成年SD大鼠36只,隨機(jī)分為正常對(duì)照組12只與實(shí)驗(yàn)組24只;正常對(duì)照組喂以普通基礎(chǔ)飼料,實(shí)驗(yàn)組應(yīng)用高脂飼料喂養(yǎng)。實(shí)驗(yàn)12周末時(shí)將造模成功的實(shí)驗(yàn)組大鼠隨機(jī)分為模型組與蛻皮甾酮治療組2個(gè)亞組,每組12只;正常對(duì)照組喂以普通基礎(chǔ)飼料至16周,模型組繼續(xù)應(yīng)用改良高脂飼料喂養(yǎng)至16周,蛻皮甾酮治療組大鼠在高脂飲食同時(shí)加用蛻皮甾酮灌胃。實(shí)驗(yàn)16周末時(shí)處死3組所有大鼠;檢測(cè)肝臟指數(shù),血清與肝組織生化指標(biāo)及肝組織病理改變;ELISA法檢測(cè)肝臟TNFα水平;免疫組化檢測(cè)各組大鼠肝組織中核因子κB蛋白表達(dá)情況。 結(jié)果 :蛻皮甾酮治療組血清膽固醇(TC)、丙氨酸氨基轉(zhuǎn)移酶(ALT)和天門冬氨酸氨基轉(zhuǎn)移酶(AST)明顯低于模型組(212±058比263±024,Plt;005;5336±1848比8460±3627,P<005;14020±3595比24359±3638,P<001);蛻皮甾酮治療組與模型組相比肝組織丙二醛(MDA)水平降低明顯(18454±1645比23928±2376,P<001),超氧化物歧化酶(SOD)活力增加顯著(942±052比518±043,P<001),肝臟指數(shù)顯著降低(435±037比504±046,P<001),肝組織脂肪變性程度和炎癥活動(dòng)度明顯減輕(546±037比630±049,P<001)。蛻皮甾酮治療組與模型組相比TNFα與核因子κB水平明顯減輕(4304±748比6156±727,2465±539比4504±746,P值均<001)。 結(jié)論 :蛻皮甾酮具有改善高脂飲食誘發(fā)的非酒精性脂肪性肝病大鼠肝臟酶學(xué)功能,通過增加肝組織SOD的含量和減少M(fèi)DA的含量來減輕肝組織氧化應(yīng)激水平,減輕肝組織TNFα和核因子κB來減輕肝臟炎癥,發(fā)揮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 factoralpha (TNFα) and nuclear factor κ B (NFκB) in rats with nonalcoholic fatty liver disease of rats. Methods : A total of 36 male Sprague Dawley rats were randomly divided into two groups, who were fed with highfat diet (experimental group, n=24) and normal basic food (normal control, n=12) respectively. At the end of the 12th week, the experimental group was randomly divided into two subgroups: model group and ecdysterone group, each group contained 12 rats. From the 13th 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 16th 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 TNFα was detected by ELISA and the expression of NFκB was measured by immunohistochemical staining. Results : At the end 16th week in ecdysterone group, the serum levels of cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were reduced markedly (212±058 vs 263±024 and 5336±1848 vs 8460±3627, both P<005; 14020±3595 vs 24359±3638, P<001); the tissue content of malondialdehyde (MDA) was decreased evidently (18454±1645 vs 23928±2376, P<001), while the activity of superoxide dismutase (SOD) was enhanced notably (942±052 vs 518±043, P<001); the liver index was decreased significantly in comparison with that inmodel group (435±037 vs 504±046, P<001); the degree of fatty degeneration and inflammation were relieved dramatically (546±037 vs 630±049, P<001). The expression of TNFα and the levels of NFκB were significantly lower (4304±748 vs 6156±727 and 2465±539 vs 4504±746, both P<001) 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 factorα and NFκB.