摘要
目的:基于过氧化酶体增殖物激活受体-α(PPARα)-固醇调节元件结合蛋白1c(SREBP-1c)-脂肪酸合酶(FAS)信号通路探讨枳葛保肝降脂方含药血清对酒精性肝病L-O2肝细胞的保护作用及其脂质代谢的机制。方法:将L-O2肝细胞接种于6孔板,贴壁后分为正常对照组、模型组(2.5%乙醇处理)、美他多辛组(美他多辛含药血清加2.5%乙醇处理)、枳葛保肝降脂方低剂量组(2.5%枳葛保肝降脂方含药血清加2.5%乙醇处理)、枳葛保肝降脂方中剂量组(5.0%枳葛保肝降脂方含药血清加2.5%乙醇处理)及枳葛保肝降脂方高剂量组(10.0%枳葛保肝降脂方含药血清加2.5%乙醇处理),24 h后测定各组细胞上清液中乳酸脱氢酶(LDH)、天冬氨酸氨基转移酶(AST)水平;定量聚合酶链反应(qPCR)、蛋白质印迹法(Western blotting)测定各组细胞内PPARα、SREBP-1c、FAS、Lipin-1 mRNA及蛋白表达。结果:与正常对照组比较,模型组细胞上清液中LDH、AST含量显著升高(P<0.001);PPARαmRNA及蛋白表达水平降低,SREBP-1c、FAS、Lipin-1 mRNA及蛋白表达水平显著升高(P<0.001);与模型组比较,枳葛保肝降脂方高剂量组和美他多辛组细胞上清液LDH、AST含量均明显下降(P<0.001),PPARαmRNA及蛋白表达水平显著升高,SREBP-1c、FAS、Lipin-1 mRNA及蛋白表达水平显著下降(P<0.001)。结论:枳葛保肝降脂方对酒精性肝病的脂质代谢有改善作用,其机制可能与上调PPARα表达,减少SREBP-1c、FAS、Lipin-1表达以抑制肝细胞脂质积累有关。
Objective:To investigate the protective effect and lipid metabolism mechanism of the serum containing Zhige Baogan Jiangzhi Fang on L-O2 hepatocytes in alcoholic liver disease based on PPARα-SREBP-1c-FAS signaling pathway.Methods:L-O2 hepatocytes were inoculated in 6-well plates,and after wall attachment,they were divided into normal group,model group(2.5%ethanol treatment),positive control group(Metadoxine-containing serum plus 2.5%ethanol),Zhige Baogan Jiangzhi Fang low dose group(2.5%Zhige Baogan Jiangzhi Fang containing drug serum plus 2.5%ethanol),Zhige Baogan Jiangzhi Fang medium dose group(5.0%Zhige Baogan Jiangzhi Fang containing drug serum plus 2.5%ethanol)and Zhige Baogan Jiangzhi Fang high dose group(10.0%Zhige Baogan Jiangzhi Fang containing drug serum plus 2.5%ethanol).Lactate dehydrogenase(LDH)and aspartate aminotransferase(AST)levels were measured in the supernatant of the cells of each group after 24 h.PPARα,SREBP-1c,FAS,Lipin-1 mRNA and protein expression were determined by qPCR and Western blotting in each group of cells.Results:Compared with the normal group,the levels of LDH and AST in cell supernatant increased in the model group(P<0.001);PPARα mRNA and protein expression levels were reduced,and the mRNA and protein expression levels of SREBP-1c,FAS,Lipin-1 increased(P<0.001).In comparison with the model group,the LDH and AST levels in the cell supernatant of the Zhige Baogan Jiangzhi Fang high dose group and the Metadoxine group were significantly decreased(P<0.001).PPARα mRNA and protein expression levels were significantly increased,and SREBP-1c,FAS,Lipin-1 mRNA and protein expression levels were significantly decreased(P<0.001).Conclusion:Zhige Baogan Jiangzhi Fang has an ameliorating effect on lipid metabolism in alcoholic liver disease,and its mechanism may be related to upregulating PPARαexpression and reducing SREBP-1c,FAS and Lipin-1 expression to inhibit lipid accumulation in liver cells.
作者
李忠婷
李志
康严
刘鹏
LI Zhongting;LI Zhi;KANG Yan;LIU Peng(School of Integrated Traditional Chinese and Western Medicine,Southwest Medical University,Luzhou Sichuan 646000,China;The Affiliated Hospital of Traditional Chinese Medicine,Southwest Medical University,Luzhou Sichuan 646000,China;Key Laboratory of Integrated Traditional Chinese and Western Medicine for the Prevention and Treatment of Digestive System Diseases,Luzhou Sichuan 646000,China)
出处
《中医药导报》
2025年第8期12-16,46,共6页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
四川省科技计划项目(重点研发项目)(2022YFS0624)
四川省中医药管理局项目(2023zd008)。
