2-甲氧基雌二醇对缺血缺氧诱导的大鼠心肌细胞凋亡的影响

Effect of 2-methoxy estradiol on ischemia/hypoxia induced cardiomyocyte apoptosis in rats

目的:探讨2-甲氧基雌二醇(2ME2)对缺血缺氧诱导的大鼠心肌细胞凋亡的影响,以及可能的机制。方法:清洁级健康雄性,成年,SD大鼠40只,随机分为假手术组、模型组、溶媒组和2ME两组,每组10只,构建大鼠急性心肌梗死模型,2ME两组在大鼠苏醒3 h内按24 mg/kg剂量腹腔注射2ME2,溶媒组和模型组则给予等量的二甲基亚砜或0.9%氯化钠溶液,1次/d,连续7 d,建模后第8天时,检测各组大鼠心脏功能,TUNEL法检测各组大鼠心脏梗死区心肌细胞凋亡情况,Western blot法检测各组大鼠心脏梗死区心肌组织中HIP-1α和BNIP3蛋白表达。结果:模型组和溶媒组大鼠LVEDD和LVESD均高于假手术组,而LVEF和FS均低于假手术组(P<0.05),2ME两组大鼠LVEDD和LVESD均低于模型组和溶媒组,而LVEF和FS均高于模型组和溶媒组(P<0.05);模型组和溶媒组大鼠心脏梗死区心肌细胞凋亡率均高于假手术组(P<0.05),2ME两组大鼠心脏梗死区心肌细胞凋亡率低于模型组和溶媒组(P<0.05);模型组和溶媒组大鼠心脏梗死区心肌组织中HIP-1α和BNIP3蛋白相对表达量高于假手术组(P<0.05),2ME两组大鼠心脏梗死区心肌组织中HIP-1α和BNIP3蛋白相对表达量低于模型组和溶媒组(P<0.05)。结论:2ME2可减少缺血-再灌注损伤大鼠梗死区心肌细胞凋亡,改善心脏功能,其机制可能与抑制HIP-1α及其靶基因BNIP3表达有关。

Objective: To investigate the effect of 2-methoxy estradiol on ischemia/hypoxia induced cardiomyocyte apoptosis in rats, and possible mechanisms. Methods: Forty healthy adult male SD rats were randomly divided into sham operation group, model group, solvent group and 2 ME2 group, 10 in each group. The acute myocardial infarction model in rat was constructed. Rats in the 2 ME2 group were intraperitoneally injected with 24 mg/kg 2 ME2 after awakening within 3 h, while in the model group and solvent group were given the same amount of dimethyl sulfoxide or physiological saline, 1 time/d, continuous 7 d. 8 d after modeling, the cardiac function of rats in each group was detected. TUNEL method was used to detect myocardial apoptosis in rats with myocardial infarction in each group. Western blot was used to detect the expressions of HIP-1 and BNIP3 proteins in myocardial infarction area of rats in each group. Results: The LVEDD and LVESD in the model group and the solvent group were higher than those in the sham operation group, while the LVEF and FS were lower than those in the sham operation group(P<0.05). The LVEDD and LVESD in the 2 ME2 group were lower than those in the model group and the solvent group, while the LVEF and FS were higher than those in the model group and the solvent group(P<0.05). The apoptosis rate of myocardial cells in myocardial infarction areas in the model group and the solvent group were higher than that in the sham operation group(P<0.05). The apoptosis rate of myocardial cells in myocardial infarction area in the 2 ME2 group was lower than that in the model group and the solvent group(P<0.05). The relative expression levels of HIP-1 a and BNIP3 proteins in myocardial infarction area in the model group and the solvent group were higher than those in the sham operation group(P<0.05). The relative expression levels of HIP-1 a and BNIP3 proteins in myocardial infarction area in the 2 ME2 group were lower than those in the model group and the solvent group(P<0.05). Conclusions: 2 ME2 could reduce the apoptosis of myocardial cells and improve cardiac function in ischemic reperfusion injury in rats. The mechanism might be related to the inhibition of the expressions of HIP-1α and its target gene BNIP3.