基于AMPK信号通路探究樱桃李多酚提取物对胰岛素抵抗HepG2细胞糖代谢的作用  

Effects of Prunus cerasifera Ehrh.polyphenol extract on glucose metabo⁃lism in insulin-resistant HepG2 cells based on AMPK signaling pathway

作　　者：苏黑艳·帕尔哈提 张姣姣 王俊人 赵家琪 李艳红[1] Suheiyan PAERHATI;ZHANG Jiaojiao;WANG Junren;ZHAO Jiaqi;LI Yanhong(Key Laboratory of Special Environment Biodiversity Application and Regulation in Xinjiang,Xinjiang Key Laboratory of Special Species Conservation and Regulatory Biology,College of Life Sciences,Xinjiang Normal University,Urumqi 830054,China)

机构地区：[1]新疆特殊环境物种多样性应用与调控实验室,新疆特殊环境物种保护与调控生物学实验室,新疆师范大学生命科学学院,新疆乌鲁木齐830054

出　　处：《中国病理生理杂志》2023年第12期2234-2241,共8页Chinese Journal of Pathophysiology

基　　金：新疆维吾尔自治区自然科学基金面上项目(No.2022D01A100);新疆维吾尔自治区高校科研计划项目(No.XJEDU2023J031);新疆师范大学重点实验室招标课题(No.XJTSWZ-2021-01);新疆师范大学2022年硕士研究生科研创新项目(No.XSY202201008)。

摘　　要：目的:探讨樱桃李多酚提取物(PCE)对胰岛素抵抗HepG2(IR-HepG2)细胞糖代谢的影响。方法:利用高糖高胰岛素诱导建立IR-HepG2细胞模型;设立对照组、胰岛素抵抗(IR)模型组、不同浓度的樱桃李多酚提取物处理组和二甲双胍组。分别以50、100、200、400 mg/L的PCE处理细胞24 h,检测其对细胞葡萄糖消耗的影响,同时利用MTT比色法评价细胞活力;采用real-time PCR和Western blot检测糖代谢相关因子mRNA及蛋白的表达。结果:樱桃李多酚提取物能够显著提高IR-HepG2细胞葡萄糖消耗,随其浓度的增加细胞活力呈先上升后下降的趋势;在mRNA及蛋白水平,除显著上调IR-HepG2细胞磷酸化AMP活化蛋白激酶(p-AMPK)蛋白表达外,糖原合成和糖异生途径中糖原合成激酶3β(GSK3β)、叉头蛋白O1(FoxO1)、过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)、葡萄糖-6-磷酸酶(G6Pase)及磷酸烯醇式丙酮酸羧激酶(PEPCK)的表达均显著下调(P<0.05)。结论:樱桃李多酚提取物能够激活IR-HepG2细胞AMPK信号通路,进一步抑制糖异生、糖原合成途径,从而改善HepG2细胞的胰岛素抵抗状态。AIM:To investigate the effects of Prunus cerasifera Ehrh.polyphenol extract(PCE)on glucose metabolism in insulin-resistant HepG2(IR-HepG2)cells.METHODS:An IR-HepG2 cells model was established using high sugar and high insulin induction;a control group,an insulin resistance(IR)model group,a PCE treatment group with different concentrations,and a metformin treatment group were set up.Cells were treated with 50,100,200,and 400 mg/L of polyphenol extract for 24 hours,respectively,to detect their effects on cellular glucose consumption.At the same time,use thiazole blue(MTT)colorimetry to evaluate cell viability.Real-time PCR and Western blot were used to detect expression of glucose metabolism-related mRNA and proteins.RESULTS:Prunus cerasifera Ehrh.polyphenol ex-tract can significantly increase glucose consumption in IR-HepG2 cells,and cell activity tends to increase and then decline as its concentration increases;At mRNA and protein levels,in addition to significantly increasing the expression of phos-phorylated adenosine monophosphate activated protein kinase(p-AMPK)protein in IR-HepG2 cells,it also decrease gly-cogen synthase kinase 3β(GSK3β)in glycogen synthesis and gluconeogenesis pathways,forked protein O1(FoxO1),peroxisome proliferator activates gamma co-receptor activation 1-alpha(PGC-1α),glucose-6-phosphatase(G6Pase)and phosphoenol pyruvate carboxykinase(PEPCK)expression.CONCLUSION:Prunus cerasifera Ehrh.polyphenol extract can activate the AMPK signaling pathway in IR-HepG2 cells,to further inhibit gluconeogenesis and glycogen synthesis pathways,thereby improving the insulin resistance state of HepG2 cells.

关 键 词：樱桃李多酚提取物 HepG2细胞 胰岛素抵抗 糖代谢 AMP活化蛋白激酶 

分 类 号：R363.2[医药卫生—病理学] R587.1[医药卫生—基础医学]