Objective To explore the effect of high glucose on mitochondrial dysfunction in H9C2 rat cardiomyocytes and the molecular mechanism of high glucose-related cardiomyopathy.Methods H9C2 rat cardiomyocytes were divided into low concentration group (5 mmol/L glucose),moderate concentration group (15mmol/L glucose) and high concentration group (30 mmol/L glucose).After treatment with glucose for 12 h,the cell viability was measured by CCK-8,the level of mitochondrial ROS was detected by mitochondrial ROS fluorescence probe,the mitochondrial membrane potential was examined by JC-1,and the related proteins levels in H9C2 rat cardiomyocytes were analyzed by Western blot.Results Compared with low concentration group,the cellular viability decreased by 14.5 percentage in moderate concentration group (P ＜ 0.05) and 26.3 percentage in high concentration group (P ＜ 0.01).Compared with low concentration group,the level of mitochondrial ROS was increased in moderate concentration group(P ＜ 0.05) and high concentration group(P＜ 0.01).Mitochondrial membrane potential of H9C2 rat cardiomyocytes maintained a high level in low concentration group,while mitochondrial membrane potential significantly decreased in moderate concentration group and high concentration group.Compared with control group,the expression of Bax/Bcl-2,cytoplasmic Cyt C and cleaved caspase-3 were significantly increased in moderate concentration group (P ＜ 0.05) and high concentration group (P ＜ 0.01).Conclusion High glucose-induced mitochondrial dysfunction may contribute to the decrease of cellular viability,suggesting that the mitochondrial dysfunction induced by high glucose might be responsible for the development of high glucose-related cardiomyopathy.%目的 观察高糖对H9C2大鼠心肌细胞线粒体功能的影响,以探讨高糖所致心肌病发生发展的分子机制. 方法 将H9C2大鼠心肌细胞分为低浓度组(含5 mmol/L葡萄糖),中浓度组(含15 mmol/L葡萄糖)和高浓度组(含30 mmol/L葡萄糖),实验干预12 h.CCK-8检测心肌细胞活力.JC-1检测心肌细胞线粒体膜电位.线粒体ROS荧光探针检测线粒体ROS水平.Western blot检测心肌细胞Bcl-2、Bax、胞质内细胞色素C(Cyt C)及cleaved caspase-3表达水平. 结果 与低浓度组相比,中浓度组心肌细胞活力降低14.5％ (P＜0.05),高浓度组心肌细胞活力降低26.3％ (P＜0.01).低浓度组心肌细胞维持较高线粒体膜电位水平,中浓度组及高浓度组心肌细胞线粒体膜电位明显降低.与低浓度组相比,中浓度组心肌细胞线粒体内ROS水平明显降低(P＜0.05),高浓度组心肌细胞线粒体内ROS水平显著降低(P＜0.01).与低浓度组相比,中浓度组心肌细胞Bax/Bcl-2、胞质内Cyt C及cleaved caspase-3表达明显升高(P＜0.05),高浓度组心肌细胞Bax/Bel-2、胞质内细胞色素C及cleaved caspase-3表达显著升高(P＜0.01). 结论 高糖导致心肌细胞线粒体功能障碍,促进了心肌细胞活力降低,可能是高糖所致心肌病分子机制之一.
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