解偶联蛋白2对高糖高脂高尿酸诱导的心肌细胞凋亡的作用及机制

发布时间：2018-02-28 04:56

本文关键词： 高尿酸血症糖尿病解偶联蛋白氧化应激心肌细胞　出处：《解放军医学杂志》2017年06期 　论文类型：期刊论文

【摘要】：目的研究解偶联蛋白2(UCP2)在高糖高脂高尿酸小鼠心肌细胞(MCM)中的作用及机制。方法以25mmol/L高糖培养基+300μmol/L软脂酸钠干预MCM 18h模拟合并高脂血症的2型糖尿病组(高糖+高脂组),在糖尿病组的基础上再用1500μmol/L尿酸干预18h模拟2型糖尿病合并高尿酸组(高糖+高脂+高尿酸组)。随后,采用UCP2抑制剂Genipin抑制心肌线粒体UCP2表达,进一步将2型糖尿病合并高尿酸组分为溶媒对照组、Genipin组。研究UCP2在高糖高脂合并高尿酸心肌细胞损伤的机制时,再分为Genipin组、Genipin+N-乙酰半胱氨酸(NAC)组。采用流式细胞仪检测各组心肌细胞的凋亡水平,q-PCR法和Western blotting检测心肌细胞中UCP2的表达情况,DHE染色及ELISA法检测活性氧簇(ROS)水平。结果与高糖+高脂组比较,高糖+高脂+高尿酸组心肌细胞凋亡明显增加(P0.05),心肌细胞中UCP2的表达水平明显降低,同时ROS的水平明显上升(P0.05)。采用Genipin抑制UCP2的表达水平后,高糖高脂高尿酸干预后心肌细胞凋亡水平及ROS水平升高更加明显(P0.05)。在此基础上应用抗氧化剂NAC后,高尿酸所诱导的心肌细胞凋亡及ROS升高被明显逆转(P0.05)。结论 UCP2可以通过抑制氧化应激缓解高糖高脂合并高尿酸所诱导的心肌细胞凋亡。
[Abstract]:Objective to study the role and mechanism of uncoupling protein 2 (UCP2) in cardiac myocytes of mice with high glucose, high lipid and high uric acid. Methods the MCM 18 h model of type 2 diabetes mellitus with hyperlipidemia (hyperglycemia) was induced by intervention of 300渭 mol/L sodium palmitate on 25mmol / L high glucose medium. Hyperlipidemia group was treated with 1 500 渭 mol/L uric acid for 18 h to simulate type 2 diabetes mellitus with high uric acid (high glucose, high fat and high uric acid group). Genipin, a UCP2 inhibitor, was used to inhibit the expression of mitochondrial UCP2 in myocardium. Type 2 diabetes mellitus with hyperuricemia was further divided into two groups: control group. The mechanism of hyperglycemia and hyperuricemia induced by UCP2 was studied. The apoptosis level of cardiac myocytes was detected by flow cytometry and the expression of UCP2 in cardiac myocytes was detected by Western blotting. The level of reactive oxygen species (Ros) was detected by ELISA method. Results compared with high glucose and high fat group, In high glucose, high lipid and high uric acid groups, the apoptosis of cardiac myocytes increased significantly, while the expression of UCP2 in cardiac myocytes decreased, while the level of ROS increased significantly. Genipin inhibited the expression of UCP2. After intervention with high glucose, high fat and high uric acid, the levels of cardiomyocyte apoptosis and ROS increased more obviously. On this basis, the antioxidant NAC was applied. The apoptosis of cardiomyocytes induced by high uric acid and the increase of ROS were obviously reversed by P0.05.Conclusion UCP2 can alleviate the apoptosis induced by high glucose and high lipid combined with high uric acid by inhibiting oxidative stress.
【作者单位】：西南医科大学临床医学院;成都军区总医院心血管内科;
【基金】：国家自然科学基金(81500208) 四川省科技厅杰出青年基金(2017JQ0012) 四川省科技支持计划项目(2015JY0277) 博士后医院管理基金(41732BA)~~
【分类号】：R587.2

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