硫氢化钠减轻高糖高脂诱导的大鼠心肌细胞系H9C2线粒体损伤  

Sodium hydrosulfide alleviates mitochondrial injury of rat myocardial cell line H9C2 induced by high glucose and high fat

作　　者：张伟才[1] 刘肆仁[1] 王尚农[2] ZHANG Weicai;LIU Siren;WANG Shangnong(Department of Cardiology,Beijing No.6 Hospital,Beijing 100070,China;Department of Endocrinology,Beijing No.6 Hospital,Beijing 100070,China)

机构地区：[1]北京市第六医院心内科,北京100070 [2]北京市第六医院内分泌科,北京100070

出　　处：《基础医学与临床》2023年第12期1834-1840,共7页Basic and Clinical Medicine

摘　　要：目的探究高糖高脂条件下硫氢化钠(NaHS)调控大鼠心肌细胞系H9C2线粒体融合/分裂的作用机制。方法采用db/db小鼠及高糖高脂(40 mmol/L葡萄糖+200μmol/L棕榈酸盐+200μmol/L油酸)处理的H9C2为2型糖尿病动物和细胞模型,分别用硫氢化钠(H 2S供体)(100μmol/L)和帕金森病相关蛋白7(DJ-1)siRNA处理48 h干预模型。心动超声和电镜分别观察心脏功能和心肌超微结构;Western blot检测CSE,Mfn2,DJ-1蛋白的表达;用MitoTracker Green探针染色观察线粒体形态变化。结果与正常对照组比高糖高脂组中线粒体分裂增加,线粒体融合降低,Mfn2的表达下降(P<0.05),Fis1表达增加(P<0.05);NaHS上调DJ-1的表达,减轻线粒体的分裂和增加Mfn2的表达水平,降低Fis1的表达。NaHS恢复db/db小鼠的心肌收缩力,减轻心肌线粒体肿胀及分裂。结论NaHS可能通过促进线粒体融合,减轻线粒体损伤。Objective To investigate the function of sodium hydrosulfide(NaHS)to regulate mitochondrial fusion/fission in diabetic cardiomyopathy and underlying mechanism.Methods Db/db mice as type 2 diabetes animal model were treated by NaHS.H9C2 cells incubated with glucose(40 mmol/L),palmitic acid(200μmol/L,Pal)and oleate(200μmol/L,Ole)were intervened by NaHS(100μmol/L).H2C9 cells were divided into control,HG+Pal+Ole,HG+Pal+Ole+NaHS and Pal+Ole+DJ-1 siRNA+NaHS groups.The protein level of Mfn2,Fis1,CSE,and DJ-1 was determined by Western blot.Mitotracker staining was used to observe the morphology of mitochondria.The ultra-structural alteration of cardiac tissues was detected by transmission electron microscopy.The cardiac functions were detected by echocardiography.Results Expression of Fis1 was increased(P<0.05)and expression of Mfn2 was decreased(P<0.05)in db/db and H9C2 treated by HG+Pal+Ole compared to control group.NaHS could upregulate the expression DJ-1,enhance the expression of Mfn2,and reduce the expression of Fis1.In db/db mice,cardiac systolic function was reduced.Disordered arrangement of myofilament,loss of cristae and mitochondrial fission were observed.NaHS could ameliorate these alterations.Conclusions NaHS may alleviate mitochondria injury by promoting mitochondrial fusion.

关 键 词：糖尿病心肌病 硫氢化钠 线粒体融合/分裂 

分 类 号：R542.2[医药卫生—心血管疾病] R587.2[医药卫生—内科学]