葡多酚通过缓解内质网应激改善胰岛β细胞功能的机制  

Grape procyanidins ameliorate insulin resistance and improve β-cell function via attenuation of endoplasmic reticulum stress

作　　者：王胜麟 肖武[1] 张海峰 

机构地区：[1]武汉市第一医院药学部,湖北武汉430022 [2]中山大学孙逸仙纪念医院 [3]广东省心电生理与心律失常实验室

出　　处：《中国老年学杂志》2017年第18期4432-4434,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金项目(81300071);广东省自然科学基金项目(2014A030313049);广东省医学科研基金项目(A2014229;A2015019;A2016270);广州市科技计划项目(201510010048;201510010050)

摘　　要：目的探讨葡多酚对胰岛素抵抗和胰岛β细胞功能的影响及机制。方法从克伦生葡萄提取葡多酚后干预高脂(HDF)喂养小鼠和胰岛β细胞株Min-6,检测内质网应激标志蛋白葡萄糖调节蛋白(GRP)-78、CCAAT/增强子结合蛋白同源蛋白(CHOP)、长链非编码RNA(lncRNA)GAS5及microRNA(miR)-346表达。通过小分子RNA干扰(siRNA)下调lncRNA GAS5后验证lncRNA GAS5在葡多酚调节内质网应激和miR-346表达水平中的作用。结果葡多酚可降低HDF动物血糖并改善胰岛素抵抗;同时抑制HDF导致小鼠胰腺内质网标志物GRP-78及CHOP升高。葡多酚还上调lncRNA GAS5和下调miR-346。siRNA-lncRNA GAS5可抑制葡多酚介导的GRP-78和miR-346下调。结论葡萄酚通过抑制内质网应激改善胰岛素抵抗和胰岛β细胞,其抑制内质网应激是通过上调lncRNA GAS5继而下调miR-346实现的。Objective To explore the effects of grape procyanidins（ GPC） on insulin resistance（ IR） and β-cell function.Methods GPC was extracted from plants（ crimson grape）,which was administrated to HDF diet induced IR in mice. GRP-78 and CHOP were detected to reflect magnitude of endoplasmic reticulum stress（ ERS）. Long non-coding RNA GAS5（ lncRNA GAS5） and microRNA-346（ miR-346） were also measured. Small interference RNA（ siRNA） against lncRNA GAS5 was used to verify the increased levels of lncRNA GAS5 and to explore its role in GRP-78 and miR-346 regulations by GPC.Results GPC lowered blood glucose and released IR,which was accompanied by lower levels of ERS markers of GRP-78 and CHOP. Expression of lncRNA GAS5 was up-regulated while miR-346 was downregulated by GPC. siRNA-lncRNA GAS5 reversed the GRP-78 and miR-346 down-regulations by GPC. Conclusions GPC could ameliorate IR through attenuation of ERS,which is mediated by up-regulation of lncRNA GAS5 and subsequently inhibition of miR-346.

关 键 词：葡多酚 内质网应激 胰岛素抵抗 长链非编码RNA GAS5 microRNA-346 

分 类 号：R587[医药卫生—内分泌]