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蛻皮甾酮對大鼠非酒精性脂肪性肝病腫瘤壞死因子α與核因子κB表達(dá)的影響

摘要:目的: 研究蛻皮甾酮對非酒精性脂肪性肝病大鼠模型腫瘤壞死因子α(TNFα)與核因子κB(NFκB)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)分為正常對照組12只與實(shí)驗(yàn)組24只;正常對照組喂以普通基礎(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法檢測肝臟TNFα水平;免疫組化檢測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(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);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(18454±1645比23928±2376,P＜001),超氧化物歧化酶(SOD)活力增加顯著(942±052比518±043,P＜001),肝臟指數(shù)顯著降低(435±037比504±046,P＜001)，肝組織脂肪變性程度和炎癥活動(dòng)度明顯減輕(546±037比630±049,P＜001)。蛻皮甾酮治療組與模型組相比TNFα與核因子κB水平明顯減輕(4304±748比6156±727,2465±539比4504±746,P值均＜001)。 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TNFα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 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.