Emodin Ameliorates High Glucose-Induced Podocyte Apoptosis via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway  

作　　者：LIU Hong CHEN Wei-dong HU Yang-lin YANG Wen-qiang HU Tao-tao WANG Huan-lan ZHANG Yan-min 

机构地区：[1]Department of Nephrology,Wuhan No.1 Hospital,Wuhan,430022,China [2]Department of Central Laboratory,Wuhan No.1 Hospital,Wuhan,430022,China

出　　处：《Chinese Journal of Integrative Medicine》2023年第9期801-808,共8页中国结合医学杂志（英文版）

基　　金：Supported by the Chinese Medicine Research Project of Hubei Provincial Health Commission(No.ZY2019Q024);Scientific Research Project of Wuhan Municipal Health Commission(No.WX20B11);Scientific Research Project of Wuhan Municipal Health Commission(No.WZ20C01)。

摘　　要：Objective To investigate the effect of emodin on high glucose(HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to induction of adenosine-monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)-mediated autophagy in podocytes(MPC5 cells)in vitro.Methods MPC5 cells were treated with different concentrations of HG(2.5,5,10,20,40,80 and 160 mmol/L),emodin(2,4,8µmol/L),or HG(40 mmol/L)and emodin(4µmol/L)with or without rapamycin(Rap,100 nmol/L)and compound C(10µmol/L).The viability and apoptosis of MPC5 cells were detected using cell counting kit-8(CCK-8)assay and flow cytometry analysis,respectively.The expression levels of cleaved caspase-3,autophagy marker light chain 3(LC3)Ⅰ/Ⅱ,and AMPK/mTOR signaling pathway-related proteins were determined by Western blot.The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.Results HG at 20,40,80 and 160 mmol/L dose-dependently induced cell apoptosis in MPC5 cells,whereas emodin(4µmol/L)significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage(P<0.01).Emodin(4µmol/L)significantly increased LC3-Ⅱ protein expression levels and induced RFP-LC3-containing punctate structures in MPC5 cells(P<0.01).Furthermore,the protective effects of emodin were mimicked by rapamycin(100 nmol/L).Moreover,emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR.The AMPK inhibitor compound C(10µmol/L)reversed emodin-induced autophagy activation.Conclusion Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway,which might provide a potential therapeutic option for diabetic nephropathy.

关 键 词：EMODIN diabetic nephropathy AUTOPHAGY podocyte apoptosis adenosine-monophosphate-activated protein kinase/mammalian target of rapamycin signaling pathways 

分 类 号：R285[医药卫生—中药学]