二陈汤对肥胖小鼠肝脏脂代谢及AMPK/ACC/SREBP1信号通路作用机制研究

Effects of Erchen Decoction on liver lipid metabolism and AMPK/ACC/SREBP1 signaling pathway of obese mice

目的:观察二陈汤对肥胖小鼠肝组织AMPK/ACC/SREBP1信号通路的作用,并探讨其改善肝脏脂质代谢及炎性病变的作用机制。方法:将小鼠随机分为空白(Control)组、模型(Model)组、奥利司他(Orlistat)组和二陈汤(ECD)组。除Control组外,其他各组小鼠通过高脂饲料建立肥胖模型。Orlistat组和ECD组小鼠分别给予奥利司他胶囊和二陈汤,Control组和Model组小鼠给予等体积的生理盐水。计算小鼠体重、肝脏湿重和肝体比值;检测小鼠血清ALT、AST、TC、TG、LDL-C、HDL-C水平;HE染色和油红O染色分别用于观察肝组织病理形态及肝组织脂滴的变化;ELISA检测肝组织中IL-1β、IL-6、IL-8、TNF-α水平;Western bolt检测肝组织中AMPK、ACC、SREBP1及其磷酸化的蛋白表达水平。结果:与Model组比较,Orlistat组和ECD组小鼠体重、肝脏湿重及肝体比值都有所降低(P<0.01,P<0.05),且肝组织病理结构和脂滴沉积得到明显改善。与Control组比较,Model组小鼠血清ALT、AST、TC、TG、LDL-C水平升高(P<0.01),而HDL-C水平下降(P<0.01)。与Model组比较,Orlistat组和ECD组小鼠血清ALT、AST、TC、TG、LDL-C水平下降(P<0.01,P<0.05),而HDL-C水平升高(P<0.01,P<0.05)。与Control组比较,Model组小鼠肝组织中p-AMPKα/AMPKα、p-ACC/ACC的表达水平显著降低(P<0.01),而IL-1β、IL-6、IL-8、TNF-α、SREBP1的表达水平显著升高(P<0.01)。与Model组比较,Orlistat组和ECD组小鼠肝组织中p-AMPKα/AMPKα、p-ACC/ACC表达水平升高(P<0.01,P<0.05),而IL-1β、IL-6、IL-8、TNF-α、SREBP1表达水平降低(P<0.01,P<0.05)。结论:二陈汤可通过调节AMPK/ACC/SREBP1信号通路改善肥胖小鼠肝脏脂代谢紊乱。

Objective:To observe the effect of ErChen Decoction on AMPK/ACC/SREBP1 signaling pathway in liver tissue of obesity mice,and explore its mechanism of improving liver lipid metabolism and inflammatory injury.Methods:The mice were divided into control group,model group,orlistat group and ErChen Decoction group(ECD).Except for the Control group,the other groups used to establish the model of obesity by high-fat diet.Orlistat and ECD groups were given orlistat capsules and ECD,respectively,while the control group and model group were given equal volumes of normal saline.The weight,liver wet weight and liver-body ratio of mice in each group were calculated.The expression levels of ALT,AST,TC,TG,LDL-C and HDL-C in the serum of mice was detected by kits.HE staining and Oil Red O staining were employed to observe the pathological morphology of liver tissue and the changes of lipid droplets in liver tissue,respectively.ELISA was used to detect the expression levels of IL-1β,IL-6,IL-8 and TNF-αin liver tissue.Western bolt was used to detect the protein expression of AMPK,ACC and SREBP1.Results:Compared with the model group,the weight,wet weight of liver and liver-to-body ratio of mice in orlistat group and ECD group were reduced(P<0.01,P<0.05),and histopathological structure and lipid droplet deposition in liver were sig nificantly improved.Compared with the control group,the expression levels of ALT,AST,TC,TG and LDL-C in the serum of the model group mice were increased significantly(P<0.01),while the expression level of HDL-C was decreased(P<0.01).Compared with the model group,the expression levels of ALT,AST,TC,TG and LDL-C in the serum of mice in orlistat group and ECD group were decreased(P<0.01,P<0.05),while the expression level of HDL-C was increased(P<0.01,P<0.05).Compared with the control group,the levels of p-AMPKα/AMPKαand p-ACC/ACC in the liver tissue of the model group were significantly reduced(P<0.01),while the expression levels of IL-1β,IL-6,IL-8,TNF-αand SREBP1 were significantly increased(P<0.01).Compared with the model group,the levels of p-AMPKα/AMPKαand p-ACC/ACC in the liver tissues of orlistat group and ECD group were increased(P<0.01,P<0.05),while the levels of IL-1β,IL-6,IL-8,TNF-αand SREBP1 were decreased(P<0.01,P<0.05).Conclusion:ErChen Decoction could improve liver lipid metabolism disorders of obesity mice via regulating AMPK/ACC/SREBP1 signaling pathway.