蜕皮甾酮对大鼠非酒精性脂肪性肝病核因子κB与PPAR-γ mRNA表达的影响

Effects of Ecdysterone on the expression of nuclear factor kappa B and peroxisome proliferator-activated receptor gamma mRNA in non-alcoholic fatty liver disease of rats

目的研究蜕皮甾酮对非酒精性脂肪性肝病大鼠模型核因子κB与PPAR-γ mRNA表达的影响,并探索其可能的作用机制。方法采用改良高脂膳食喂养法,建立大鼠非酒精性脂肪性肝病模型。健康成年雄性SD大鼠48只,随机分为正常对照组、模型组、蜕皮甾酮处理组与吡格列酮处理组,每组12只。模型组应用改良高脂饲料喂养,蜕皮甾酮组与吡格列酮组在高脂饲料喂养同时应用药物灌胃,正常对照组应用基础饲料喂养。实验16周末,处死所有大鼠,观察检测肝脏指数、血清与肝组织生化指标及肝组织病理改变;免疫细胞化学法检测各组大鼠肝组织中核因子κB蛋白表达情况;实时荧光定量PCR技术检测PPAR-γ mRNA水平变化。结果蜕皮甾酮组和吡格列酮组血清胆固醇(TC)、甘油三酯(TG)、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(P<0.05);蜕皮甾酮和吡格列酮组与模型组相比,肝组织丙二醛(MDA)水平降低明显,超氧化物歧化酶(SOD)活力增加显著;蜕皮甾酮肝脏指数显著降低;肝组织脂肪变性程度和炎症活动度明显减轻(P<0.05)。蜕皮甾酮和吡格列酮组与模型组相比核因子κB水平明显降低(P<0.01),PPAR-γ mRNA显著增加(P<0.05)。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,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,增加肝组织PPAR-γ mRNA和减少核因子κB改善胰岛素抵抗,减轻肝脏炎症,发挥防治非酒精性脂肪性肝病的作用。

【Objective】To investigate the effect and possible mechanism of Ecdysterone in preventing nonalcoholic fatty liver disease （NAFLD） in rats.【Methods】Rat models of NAFLD were established by high-fat diet.A total of forty-eight male Sprague Dawley rats were randomly divided into four groups：fed with high-fat diet （model group）,high-fat diet plus Ecdysterone （Ecdysterone group）,high-fat diet plus Pioglitazone （Pioglitazone group） and normal basic food （normal control）.By 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 nuclear factor kappa B （NF-κB） was measured by immunohistochemical staining and the expression of PPAR-γmRNA was detected by Real-time quantitative PCR.【Results】At the end of 16th week in Ecdysterone group,the serum levels of cholesterol （TC）,triglyceride （TG）,alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were reduced markedly （P 〈0.05）;the tissue content of malondialdehyde （MDA） was decreased evidently,while the activity of superoxide dismutase （SOD） was enhanced notably;the liver index was de-creased significantly in comparison with that in model group;the degree of fatty degeneration and inflammation were relieved dramatically （P 〈0.05）.The expression of nuclear factor-κB levels were significantly lower （P 〈0.01） and the PPAR-γ mRNA increased significantly （P 〈0.05） in Ecdysterone and Pioglitazone group compared with model group.【Conclusion】The effects of Ecdysterone in preventing NAFLD in rats could be related to decrease content of MDA and nuclear factor-κB and increase content of SOD and PPAR-γ in hepatic tissue.