利拉鲁肽对高糖诱导的足细胞凋亡的影响及机制

Effect and mechanism of liraglutide on podocyte apoptosis induced by high glucose

目的:探讨利拉鲁肽对高糖诱导的足细胞凋亡的影响及机制。方法:将购买的小鼠足细胞(MPC5)分为7组:正常糖(NG)组、高糖(HG)组、甘露醇(M)组、高糖+沉默信息调节因子1(SIRT1)激动剂(HG+RSV)组、高糖+SIRT1激动剂+SIRT1阻断剂(HG+RSV+S)组、高糖+胰高血糖素样肽-1受体(GLP-1R)激动剂利拉鲁肽(HG+LG)组,高糖+胰高血糖素样肽-1受体(GLP-1R)激动剂+GLP-1R阻断剂(HG+LG+E)组。刺激72 h后,采用流式细胞术检测足细胞凋亡率;共聚焦荧光成像技术检测足细胞骨架蛋白synaptopodin表达水平;免疫印迹检测GLP-1R,SIRT1表达。结果:HG组足细胞凋亡率升高,synaptopodin,SIRT1和GLP-1R表达降低,与NG组比较,差异有统计学意义(P<0.01);HG+RSV组足细胞凋亡率降低,SIRT1表达升高,与HG组比较,差异有统计学意义(P<0.01);而SIRT1特异性拮抗剂则阻断了SIRT1激动剂对足细胞的保护作用;HG+LG组足细胞凋亡率降低,SIRT1和GLP-1R表达升高,与HG组比较差异有统计学意义(P<0.01);而GLP-1R特异性拮抗剂则阻断了GLP激动剂对SIRTI的表达调控作用。结论:高糖可诱导足细胞发生凋亡和损伤,利拉鲁肽可减少高糖诱导的足细胞凋亡,其机制可能与激活GLP-1R/SIRT1信号途径有关。

Objective:To investigate the effect of glucagon like peptide-1 receptor(GLP-1R)agonists on podocyte apoptosis induced by high glucose(HG)and its possible mechanism.Methods:According to different glucose concentrations and interventions,podocytes MPC5 cells were assigned to the following 7 groups:normal glucose group(NG),high glucose group(HG),mannitol group(MA),HG+silent information regulator 1(SIRT1)agonist group(HG+RSV),HG+SIRT1 agonist+SIRT1 inhibitor group(HG+RSV+S);HG+glucagon-like peptide-1 receptor(GLP-1R)agonist group(HG+LG),HG+GLP-1R agonist+GLP-1R inhibitor group(HG+LG+E).Podocyte apoptosis rate was assessed utilizing flow cytometry.The expression level of cytoskeletal protein synaptopodin was evaluated through the utilization of confocal fluorescence imaging technique.The expression of GLP-1R and SIRT1 was assessed using Western blot analysis.Results:High glucose increased the podocytic apoptosis rate,decreased expression of synaptopodin,SIRT1,and GLP-1R(all P<0.01).SIRT1 agonist(RSV)attenuated the podocytic apoptosis rate and upregulated SIRT1 expression,And SIRT1 specific antagonists block the protective effect of SIRT1 agonists on podocytes.The podocytic apoptosis rate was reduced by the administration of GLP-1R agonist(LG),accompanied by increased expression of both SIRT1 and GLP-1R.However,GLP-1R specific antagonists blocked the protective effect of GLP-1R agonists on podocytes.Conclusion:GLP-lR agonists prevent podocytes injury induced by High glucose.The possible mechanisms may involve the GLP-1R/SIRT1 signaling pathway.