【摘 要】
：
目的:探讨达格列净对糖尿病合并心肌缺血大鼠心肌细胞能量代谢及血液流变学的作用研究.方法:2型糖尿病雌性Go-to-Kakizaki大鼠根据实验要求分为三组:对照组,心肌缺血组和达格列净组.通过右颈总动脉血流动力学系统评估大鼠SBP、MAP和DBP;LabScribe 2软件操作的记录系统监测大鼠的心脏收缩舒张功能;TTC染色和组织学分别检测大鼠的心肌梗塞面积百分比和心肌损伤评分;TUNEL测定法测定大鼠心肌细胞凋亡;测定试剂盒和荧光追踪检测大鼠心肌中的ATP含量、ADP/ATP比率、线粒体膜电位MMP;蛋
【机 构】
：
陕西省人民医院心血管内三科 陕西西安710068;陕西省人民医院心血管内一科 陕西西安710068
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目的:探讨达格列净对糖尿病合并心肌缺血大鼠心肌细胞能量代谢及血液流变学的作用研究.方法:2型糖尿病雌性Go-to-Kakizaki大鼠根据实验要求分为三组:对照组,心肌缺血组和达格列净组.通过右颈总动脉血流动力学系统评估大鼠SBP、MAP和DBP;LabScribe 2软件操作的记录系统监测大鼠的心脏收缩舒张功能;TTC染色和组织学分别检测大鼠的心肌梗塞面积百分比和心肌损伤评分;TUNEL测定法测定大鼠心肌细胞凋亡;测定试剂盒和荧光追踪检测大鼠心肌中的ATP含量、ADP/ATP比率、线粒体膜电位MMP;蛋白印迹分析线粒体裂解融合因子线粒体蛋白2(Mitochondrial protein 2,MFN2),视神经萎缩1(Optic nerve atrophy 1,OPA1)和动力蛋白相关的蛋白1(Dynein-related protein 1,DRP1)的蛋白表达;RT-PCR分析大鼠心肌细胞中能量代谢相关因子PGC1-α和CPT-1的转录.结果:心肌缺血组较对照组的SBP、MAP升高(P＜0.05),达格列净组较心肌缺血组降低(P＜0.05),与对照组相比,心肌缺血组和达格列净组的DBP比较无差异(P＞0.05).心肌缺血组较对照组LVEF降低(P＜0.05),LVIDs、LVPWs和LVPWd升高(P＜0.05),达格列净组较心肌缺血组的LVEF升高(P＜0.05),LVIDs、LVPWs和LVPWd降低(P＜0.05).心肌缺血组较对照组的梗塞面积占比和组织损伤评分升高(P＜0.05),达格列净组较心肌缺血组梗塞面积、组织损伤评分降低(P＜0.05).与对照组相比,心肌缺血组TUNEL阳性细胞数量增多(P＜0.05).此外,与心肌缺血组相比,达格列净组的TUNEL阳性细胞数量降低(P＜0.05).线粒体膜电位MMP.心肌缺血组较对照组的ATP含量和MMP降低(P＜0.05),ADP/ATP比率升高(P＜0.05),达格列净组较心肌缺血组ATP含量和MMP升高(P＜0.05),ADP/ATP比率降低(P＜0.05).心肌缺血组较对照组MFN2和OPA1的蛋白表达降低(P＜0.05),DRP1蛋白表达升高(P＜0.05),达格列净组较心肌缺血组MFN2和OPA1的蛋白表达升高(P＜0.05),DRP1蛋白表达降低(P＜0.05).心肌缺血组较对照组PGC1-α和CPT-1的mRNA表达降低(P＜0.05),达格列净组较心肌缺血组PGC1-α和CPT-1的mRNA表达升高(P＜0.05).结论:达格列净给药可减糖尿病合并心肌缺血大鼠的心肌梗死面积,增强心室功能和心肌细胞能量代谢,发挥心脏保护作用.
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