Ang(1-7)对高糖高脂培养的胰岛β细胞自噬的影响  

Angiotensin(1-7)alleviates apoptosis inβ-cells under high-glucose and high-fat conditions by enhancing autophagy

作　　者：胡东辉 孙明谨 陆春丽 HU Donghui;SUN Mingjin;LU Chunli(Department of Reproductive Medicine,Suizhou Hospital,Hubei University of Medicine,Suizhou 441300,China;Department of Endocrinology,Suizhou Hospital,Hubei University of Medicine,Suizhou 441300,China)

机构地区：[1]湖北医药学院附属随州医院生殖医学科,湖北随州441300 [2]湖北医药学院附属随州医院内分泌科,湖北随州441300

出　　处：《中国病理生理杂志》2025年第1期136-141,共6页Chinese Journal of Pathophysiology

基　　金：湖北省科技计划大健康项目(No.2022BCE033)。

摘　　要：目的:研究血管紧张素(1-7)[Ang(1-7)]对高糖高脂培养的小鼠胰岛β细胞系MIN6细胞自噬的影响。方法:MIN6细胞分别给予DMEM培养基培养(CON组)、高糖高脂(GLT组)、Ang(1-7)+高糖高脂[Ang(1-7)+GLT组]、A779(Mas受体拮抗剂)+Ang(1-7)+高糖高脂[A779+Ang(1-7)+GLT组]、自噬抑制剂3-甲基腺嘌呤(3-MA)+Ang(1-7)+高糖高脂[3-MA+Ang(1-7)+GLT组]干预。透射电镜观察MIN6细胞自噬小体变化,免疫荧光观察MIN6细胞内自噬相关蛋白微管相关蛋白1轻链3(LC3)的表达,Western blot检测自噬相关蛋白LC3-II/LC3-I、螯合体1(P62)的表达,流式细胞术检测细胞凋亡水平。结果:与CON组相比,GLT组胞质中细胞器减少,出现大量空泡区域,可见有自噬小体分布,P62表达水平明显增加(P<0.05),细胞凋亡率明显增加(P<0.05);与GLT组相比,Ang(1-7)+GLT组自噬小体增多,胞质中空泡化现象改善明显,LC3-II/LC3-I表达明显增加(P<0.05),P62表达明显下降(P<0.05),细胞凋亡率明显降低(P<0.05);A779阻断Ang(1-7)在MIN6细胞中对自噬的影响。3-MA+Ang(1-7)+GLT组细胞凋亡率较Ang(1-7)+GLT组明显增加。结论:Ang(1-7)通过激活Mas受体促进高糖高脂培养的胰岛β细胞自噬,减轻了高糖高脂诱导的MIN6细胞凋亡和损伤。AIM:We aimed to evaluate the effect of angiotensin(Ang)(1-7)on autophagy in MIN6 cells under high-palmitate(PA)and high-glucose culture conditions.METHODS:MIN6 cells were cultured under various conditions:Dulbecco's Modified Eagle Medium(control,CON),high glucose and high PA concentrations(GLT),Ang(1-7)plus high glucose and high PA concentrations[Ang(1-7)+GLT],A779 inhibitor plus Ang(1-7)plus high glucose and high PA concentrations[A779+Ang(1-7)+GLT],and 3-methyladenine(3-MA)plus Ang(1-7)plus high glucose and high PA concentrations[3-MA+Ang(1-7)+GLT].The expression of microtubule-associated protein 1 light chain 3(LC3)was assessed using immunofluorescence,and Western blot was used to measure the expression of the autophagy-related proteins LC3-II/LC3-I and P62.Apoptosis was quantified using flow cytometry.RESULTS:GLT cells had fewer cytoplasmic organelles,more vacuolated cells,an altered autophagosome distribution,higher P62 expression(P<0.05),and greater apoptosis(P<0.05)than CON cells.Ang(1-7)+GLT cells showed greater autophagosome formation,much less cytoplasmic vacuolization,a higher LC3-II/LC3-I ratio(P<0.05),lower P62 expression(P<0.05),and less apoptosis(P<0.05)than CON cells.A779 negated the pro-autophagic effects of Ang(1-7)in the MIN6 cells.Furthermore,inhibition of autophagy with 3-MA resulted in significantly greater apoptosis in 3-MA+Ang(1-7)+GLT cells vs Ang(1-7)-treated cells.CONCLUSION:Ang(1-7)activates Mas receptors to promote autophagy in pancreaticβcells cultured under highglucose and high-fat conditions,thereby mitigating apoptosis and cellular pathology.

关 键 词：血管紧张素(1-7) Β细胞 糖脂毒性 自噬 

分 类 号：R587.1[医药卫生—内分泌] R363[医药卫生—内科学] Q578[医药卫生—临床医学]