硝酸甘油对大鼠缺氧心肌细胞乙醛脱氢酶2表达的影响  

Effect of glyceryl trinitrate on expression of aldehyde dehydrogenase 2 in hypoxia-exposed rat cardiomyocytes

作　　者：张应花[1,2] 孙爱军[1] 文小军[3] 王克强[1] 邹云增[1] 葛均波[1] 

机构地区：[1]复旦大学附属中山医院心内科,上海200032 [2]复旦大学上海医学院解剖与组织胚胎系 [3]新乡医学院基础医学院

出　　处：《上海医学》2010年第5期417-420,共4页Shanghai Medical Journal

摘　　要：目的探讨硝酸甘油(GTN)对大鼠缺氧心肌细胞凋亡的影响及其相关机制,为阐明长期使用GTN导致心脏不良事件的发病机制提供依据。方法利用心肌细胞缺氧模型,将缺氧的正常细胞作为对照组,测定GTN作用1～3d时心肌细胞的凋亡率以及乙醛脱氢酶2(ALDH2)基因和蛋白的表达。结果①1、10、100μmol/L的GTN作用1d的心肌细胞凋亡均显著少于对照组(P值均<0.05),作用2、3d的细胞凋亡数均显著高于作用1d时(P值均<0.05)。由此确定GTN的作用浓度是1μmol/L,作用时间是2d。②不同浓度GTN作用1～3d,ALDH2基因表达与心肌细胞凋亡率呈负相关(r=-0.658,P=0.028)。③1μmol/LGTN作用2d时的ALDH2蛋白表达为1.35±0.16,显著低于对照组的1.66±0.22(P<0.05);作用2、3d时的ALDH2蛋白表达分别为1.35±0.16和0.33±0.27,均较作用1d时显著下降(P值均<0.05)。结论①GTN作用不同时间所起的作用不同:作用1d,为心肌保护作用;作用2～3d能引起心肌细胞凋亡增加,缺乏心肌保护作用。②GTN使用后ALDH2基因表达变化与心肌细胞凋亡呈负相关,可能与ALDH2对缺氧心肌细胞有保护作用有关。③GTN作用2～3d时缺氧心肌细胞ALDH2 mRNA和蛋白水平下调,可能与ALDH2消耗有关。Objective To explore the effect of glyceryl trinitrate （GTN） on the apoptosis of hypoxic rat cardiomyocytes and its possible mechanism, so as to elucidate the mechanism of adverse events after long term use of GTN. Methods Using myocardial anoxia modal, we examined the apoptosis rate of hypoxic cardiomyocytes and the expression of aldehyde dehydrogenase 2 （ALDH2） mRNA and protein after GTN treatment for 1- 3 days. Normal myocardiocytes were taken as control. Results ①One day after GTN treatment, the apoptosis rate of hypoxic cardiomyocytes was lower than that in the control group, and the apoptosis rates on the 2nd and 3rd days after treatment were significantly higher than that on the Ist day after GTN treatment （ P〈0.01）. Thus 1 μmol/L and GTN use for 2 days were the optimal concentration and action time. ② The level of ALDH2 mRNA expression in hypoxic cardiomyocytes after GTN treatment was inversely correlated with the apoptosis of cardiomyocytes exposed to hypoxia （r = -0. 658, P = 0. 028）.③ The level of ALDH2 mRNA and protein in hypoxic cardiomyocytes undergoing GTN treatment for 1 - 3 days had an decreasing tendency. The level of ALDH2 protein expression of hypoxic cardiomyocytes following 2-day-GTN treatment for was significantly decreased （[1.153±0.037] vs. [1. 984 ± 0. 238], P = 0. 038〉 compared with that in the control group. ALDH2 protein expression in hypoxic cardiomyocytes on 2 or 3 days after GTN treatment was significnatly lower （ P = 0. 024, P = 0.056, respectively） than that on 1 day after GTN treatment. Conclusion ① GTN treatment for 1 day offers cardioprotection in hypoxic cardiomyocytes; however GTN treatment for 2 - 3 days induce apoptosis in cardiomyocytes. ②The level of ALDH2 mRNA after GTN treatment is negatively correlated with the apoptosis of cardiomyocytes exposed to hypoxia, which might be correlated with the cardioprotecUon of ALDH2. ③The expression of ALDH2 mRNA and protein at 2 - 3 days after GTN treatment is down-regulated, which is probabl

关 键 词：硝酸甘油 生物活化 心肌缺氧 乙醛脱氢酶2 细胞凋亡 

分 类 号：R965[医药卫生—药理学]