视神经萎缩症蛋白1通过抑制氧化应激减少高糖高脂诱导的心肌细胞凋亡

发布时间：2018-03-19 01:30

本文选题：糖尿病　切入点：高脂　出处：《第三军医大学学报》2017年02期 　论文类型：期刊论文

【摘要】：目的研究高糖高脂对心肌细胞的影响及视神经萎缩症蛋白1(optical atrophy-1,OPA1)在其中的具体作用。方法将高糖培养基培养的小鼠心肌细胞分为3组:高糖+0、200、400μmol/L软脂酸钠组,并分别干预8 h和16 h。采用si RNA敲低心肌OPA1表达,进一步将400μmol/L软脂酸钠组分为对照组、OPA1 si RNA干预组、Scra si RNA干预组、OPA1 si RNA+NAC干预组。通过流式细胞仪检测各组心肌细胞在不同时间点的凋亡水平,q-PCR法检测心肌细胞中OPA1m RNA的表达情况,DHE染色法与ELISA试剂盒测定心肌细胞中活性氧簇(reactive oxygen species,ROS)水平。结果心肌细胞凋亡水平随着软脂酸钠的浓度和干预时间逐渐增加(P0.05)。与对照组相比,高脂干预明显抑制心肌细胞中OPA1的表达,同时显著地促进ROS生成(P0.05)。通过OPA1 si RNA干扰OPA1的表达水平后,高脂诱导的心肌细胞凋亡与ROS生成进一步增加(P0.05);相反地,抗氧化剂N-乙酰半胱氨酸(N-acetyl-L-cysteine,NAC)逆转了上述OPA1抑制所导致的心肌细胞凋亡。结论高脂血症会进一步增加糖尿病心肌细胞的易损性,OPA1可以通过抑制氧化应激反应促进伴有高脂血症糖尿病条件下的心肌细胞存活。
[Abstract]:Objective to study the effects of hyperglycemia and hyperlipidemia on cardiomyocytes and the specific effect of optic nerve atrophy protein 1 optical atrophy-1 (OPA1). Methods cultured cardiomyocytes in high glucose medium were divided into three groups: high glucose 0,200,400 渭 mol/L sodium palmitate group. Si RNA knockout was used to lower the expression of OPA1 in myocardium after 8 h and 16 h intervention, respectively. Further, 400 渭 mol/L sodium palmitate was divided into control group (OPA1 si RNA intervention group) and Scra si RNA RNA intervention group (OPA1 si RNA NAC intervention group). Flow cytometry was used to detect the apoptosis level of cardiac myocytes at different time points. The expression of OPA1m RNA was determined by DHE staining and ELISA kit. Results the apoptosis level of cardiomyocytes increased with the concentration and intervention time of sodium palmitate. Hyperlipidemia significantly inhibited the expression of OPA1 in cardiomyocytes and significantly promoted the production of ROS by P0.05. after OPA1 si RNA interfered with the expression of OPA1, the apoptosis and ROS production of cardiomyocytes induced by hyperlipidemia were further increased. The antioxidant N-acetyl-L-cysteine (Nacetyl-L-cysteine) reversed the cardiomyocyte apoptosis induced by the inhibition of OPA1. Conclusion Hyperlipidemia may further increase the vulnerability of diabetic cardiomyocytes to OPA1 by inhibiting oxidative stress. Cardiomyocytes with hyperlipidemia and diabetes survived.
【作者单位】：第三军医大学研究生管理大队;成都军区总医院心血管内科;
【基金】：国家自然科学基金青年科学基金(81500208) 全军医学科技青年培育项目(14QNP050) 四川省科技支持计划项目(2015JY0277)~~
【分类号】：R587.2;R54

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