解偶联蛋白2通过抗氧化应激反应预防酒精性心肌损害

Uncoupling Protein 2 Attenuates Alcohol-induced Damage in Cardiomyocyte via Its Antioxidative Effects

目的:探讨解偶联蛋白2(uncoupling protein 2,UCP2)在酒精性心肌损害中的作用及其分子机制。方法:采用乙醇在体内的代谢产物乙醛作为刺激因素,将培养心肌细胞分为对照组,乙醛组和乙醛+UCP2抑制剂京尼平组(京尼平组),干预24小时后检测心肌细胞中超氧阴离子(superoxide anion,SOA)及一氧化氮(nitric oxide,NO)的水平,并检测UCP2的蛋白表达水平,另一组实验干预72小时后采用TUNEL法检测心肌细胞凋亡率。结果:与对照组比较,乙醛组心肌细胞中SOA水平显著升高(P<0.01),而NO水平显著降低(P<0.01),且UCP2的蛋白水平也较对照组显著增加(P<0.01)。而与乙醛组比较,京尼平组心肌细胞中SOA的水平进一步增加(P<0.01),NO的水平也进一步降低(P<0.01)。与对照组比较,乙醛可诱导培养心肌细胞凋亡(P<0.01),而京尼平组凋亡率较乙醛组则进一步升高(P<0.01)。结论:UCP2在酒精性心肌损害中通过调控SOA/NO的水平发挥代偿性保护作用。

Objective： To investigate the effect of uncoupling protein 2 （UCP2） on alcohol-induced damage in cardiomyocyte and the underlying molecular mechanisms. Methods：Acetaldehyde was used as the stimulus. Primary cultured cardiomyocytes were divided into three groups： control group, acetaldehyde group, and acetaldehyde plus genipin group. After incubation for 24 hours, the level of superoxide anion （SOA） and nitric oxide （NO） were detected; the protein expression of UCP2 was measured. After incubation for 72 hours, the apoptotic rate was detected by TUNEL staining. Results：Acetaldehyde incubation for 24 hours caused a significant increase in SOA level and a significant decrease in NO level （both P〈0.01） and remarkably upregulated UCP2 in cultured cardiomyocyte（P〈0.01）. Treatment with UCP2 inhibitor genipin further enhanced acetaldehyde-induced increase in SOA level and decrease in NO level（both P〈0. 01）. Alcohol incubation for 72 hours caused a significant increase in apoptotic rate of cardiomyocyte （P〈0.01）. Moreover, treatment with genipin further enhanced acetaldehyde-induced apoptosis of cardiomyocyte （P〈0.01）. Conclusion：UCP2 might provide a compensatory protective effect on alcohol-induced damage in cardiomyocyte through regulating the levels of SOA and NO.