【摘要】 目的观察白藜芦醇(RSV)对Lieber-De Carli酒精液体饲料诱导的小鼠酒精性脂肪肝的作用,并初步探讨其可能的相关分子机制。方法 6~8周龄雄性C57BL/6J小鼠随机分为6组:正常对照组、模型组、RSV(10、30、100 mg/kg)组和谷胱甘肽(GSH,200 mg/kg)阳性对照组,造模的同时给予药物干预共10 d,实验结束后称取体重,处死小鼠,收集血液和肝脏,分离血清测定相关指标,病理切片观察肝脏的脂肪蓄积,免疫组化法检测脂肪分化相关蛋白(ADRP)的表达,Western blot法检测肝脏腺苷酸激活蛋白激酶(AMPK)及脂素(lipin1)的表达。结果与模型组比较,RSV组血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)水平显著降低(P<0.01),但血清三酰甘油(TG)水平降低不明显;肝脏TG(低剂量:P<0.05,中、高剂量:P<0.01)和丙二醛(MDA)含量显著降低(P<0.01),超氧化物歧化酶(SOD)活性显著升高(P<0.01)。病理组织学结果显示RSV明显减轻肝脏脂肪变性,免疫组化法结果显示RSV能够抑制ADRP的表达,Western blot法结果表明RSV能激活AMPK活性,增加其磷酸化水平,并能抑制lipin1蛋白的表达。结论 RSV对小鼠酒精性脂肪肝具有一定的保护作用,其机制可能与激活AMPK-lipin1通路有关。更多还原

【Abstract】 Objective To evaluate the protective effects of resveratrol( RSV) on alcoholic fatty liver( AFL) mice,and investigate the potential molecular mechanism. Methods We conducted vivo studies in C57 BL /6J mice fed with ethanol Lieber-De Carli liquid diet and treated with RSV( 10,30,100 mg / kg) and GSH( 200 mg / kg). Results The results showed that RSV( 30 or 100 mg / kg) treatment significantly attenuated hepatic steatosis with lowering activities of serum alanine aminotransferase( ALT),aspartate aminotransferase( AST) and levels of hepatic triglyceride( TG),increasing superoxide dismutase( SOD) activities,decreasing malondialdehyde( MDA)content,although the levels of serum TG were not changed significantly. Immunohistochemistry analysis and HE staining showed that RSV suppressed the expression of adipose differentiation-related protein( ADRP) and reduced hepatic lipid accumulation. Western blot analysis showed that RSV stimulated AMP-activated protein kinase( AMPK) activity and inhibited lipin1 expression. Conclusion RSV has protective effects on alcoholic fatty liver,and the potential mechanism might be involved in activation of AMPK-lipin1 signaling and its antioxidant roles.更多还原