阿魏酸抑制p38 MAPK保护棕榈酸诱导的肝细胞脂毒性  

Ferulic acid protects palmitic acid-induced lipotoxicity in hepatocytes via inhibiting p38 MAPK

作　　者：傅爱 徐甜甜 杨贞[2,3] 韩强 窦晓兵 李松涛[1,3] FU Ai;XU Tiantian;YANG Zhen;HAN Qiang;DOU Xiaobing;LI Songtao(School of Basic Medicine&Public Health,Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China;School of Life Science,Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China;Institute of Molecular Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China)

机构地区：[1]浙江中医药大学基础医学院、公共卫生学院,浙江杭州310053 [2]浙江中医药大学生命科学学院,浙江杭州310053 [3]浙江中医药大学分子医学研究所,浙江杭州310053

出　　处：《中国临床药理学与治疗学》2021年第2期137-143,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金(81773422,81573132);浙江省杰出青年基金(LR20H260001);浙江省中西医结合循环系疾病诊治重点实验室开放基金(2C32006)。

摘　　要：目的:研究阿魏酸对棕榈酸诱导的HepG2肝细胞脂毒性的保护作用并初步探究其分子机制。方法:采用棕榈酸诱导HepG2肝细胞建立脂毒性模型并给予阿魏酸进行干预,采用LDH法检测细胞损伤,采用MTT法检测细胞存活率。采用Western Blotting技术对阿魏酸保护作用的分子机制进行研究。结果:不同浓度(25、50、100、200μmol/L)阿魏酸暴露对肝细胞无毒性作用(P>0.05)。阿魏酸干预显著抑制棕榈酸诱导的肝细胞损伤并改善棕榈酸诱导的细胞线粒体膜电位降低(P<0.05)。激活p38可显著增强棕榈酸诱导的肝细胞脂毒性(P<0.05),而抑制p38显著改善棕榈酸诱导的细胞损伤(P<0.05)。此外,阿魏酸显著抑制棕榈酸上调的p38磷酸化(P<0.05),采用p38激活剂处理细胞可阻断阿魏酸对脂毒性的保护作用(P<0.05)。结论:阿魏酸可有效改善脂毒性诱导的肝细胞损伤,该保护作用可能与其抑制p38信号通路有关。阿魏酸可能成为防治以脂毒性为主要病理特征性肝病的功效因子。AIM:To investigate the protective effect of ferulic acid on palmitic acid-induced lipotoxicity in HepG2 cells and to explore its potential molecular mechanisms.METHODS:HepG2 cells were induced by palmitic acid to establish a lipotoxicity model,while ferulic acid was added prior to palmitic acid treatment.Lactate dehydrogenase(LDH)was used to detect cell damage.Methyl azozole trace enzyme reaction is used for 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)was employed to detect cell viability.The molecular mechanisms of the protective effect of ferulic acid was analyzed by Western Blotting.RESULTS:There was no cytotoxic effect of different concentrations of ferulic acid(25,50,100,200μmol/L)treatment on HepG2 cells(P>0.05).Ferulic acid intervention significantly inhibited palmitic acid-induced cell death and improved palmitic acid-induced reduction of cell mitochondrial membrane potential(P<0.05).The activation of p38 significantly enhanced palmitic acid-induced hepatocellular lipotoxicity(P<0.05),while inhibition of p38 significantly improved palmitic acid-induced cell damage(P<0.05).In addition,ferulic acid significantly inhibited the upregulation of p38 phosphorylation by palmitic acid treatment(P<0.05).p38 activator exposure blocked the protective effect of ferulic acid on lipotoxicity(P<0.05).CONCLUSION:Ferulic acid effectively improves hepatocellular injury induced by lipotoxicity.The inhibition of p38 signaling pathway is potentially involved in its protective effect.Ferulic acid may be an effective factor in the prevention and treatment of liver disease with lipotoxicity as a major pathological characteristic.

关 键 词：阿魏酸 棕榈酸 P38 脂毒性 肝细胞 

分 类 号：R965.2[医药卫生—药理学]