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目的观察重组人红细胞生成素(rHu-EPO)对大鼠心肌梗死的治疗作用并探讨其机制。方法体外培养出生3 d 内 SD 大鼠心肌细胞,缺氧培养和 H_2O_2模拟氧化应激反应诱导凋亡,培养体系中加入 rHu-EPO,荧光染色观察凋亡率的变化。32只成年 SD 大鼠分空白组8只、心肌梗死组12只和治疗组12只;空白组开胸但不结扎冠脉,心肌梗死组和治疗组结扎左冠前降支制备心肌梗死的模型,治疗组每天腹腔注射5000 IU/kg rHu-EPO 共7 d,14 d 后所有大鼠检测血流动力学指标,心脏切片原位末端标记(TUNEL)检测凋亡,免疫组化检测 Bcl-2、Bax 表达。结果 rHu-EPO 使心肌细胞缺氧诱导的凋亡率由47.92%±5.87%下降为28.21%±4.35%;氧化应激反应所诱导的凋亡率由60.42%±5.54%下降为43.40%±5.39%;腹腔注射 rHu-EPO 使得心肌梗死后大鼠心功能保存较好,动脉收缩压、平均动脉压、左心室收缩压、±dp/dt_(max)都有所提高,同时,左心室舒张压、左心室舒张末期压下降;细胞凋亡率由1.65%±0.50%减少为0.84%±0.30%;Bcl-2蛋白表达率由0.96%±0.37%增加为1.43%±0.28%;Bax 蛋白表达率由1.34%±0.47%减少为0.68%±0.30%。结论rHu-EPO 可抑制心肌细胞凋亡、保存心功能,可能是通过下调 Bax 表达和上调 bcl-2表达实现的。
Objective To observe the therapeutic effect of recombinant human erythropoietin (rHu-EPO) on myocardial infarction in rats and its mechanism. Methods SD rat cardiomyocytes were cultured in vitro for 3 days. Hypoxia and H 2 O 2 simulated oxidative stress induced apoptosis in vitro. RHu-EPO was added to the culture system to observe the changes of apoptosis rate. Thirty-two adult SD rats were divided into blank group (n = 8), myocardial infarction group (n = 12) and treatment group (n = 12). The rats in the blank group underwent thoracotomy without coronary artery ligation and myocardial infarction . The rats in the treatment group were injected intraperitoneally with 5000 IU / kg rHu-EPO for 7 days. After 14 days, all the rats were examined for hemodynamics, TUNEL assay and Bcl-2 immunohistochemistry , Bax expression. Results The apoptotic rate induced by hypoxia of cardiomyocytes decreased from 47.92% ± 5.87% to 28.21% ± 4.35% in rHu-EPO group, and decreased from 60.42% ± 5.54% to 43.40% ± 5.39 %. After intraperitoneal injection of rHu-EPO, the cardiac function of rats after myocardial infarction was well preserved. Arterial systolic pressure, mean arterial pressure, systolic pressure of left ventricle and ± dp / dt max increased, meanwhile, left ventricular diastolic pressure , Left ventricular end diastolic pressure decreased; apoptosis rate decreased from 1.65% ± 0.50% to 0.84% ± 0.30%; Bcl-2 protein expression increased from 0.96% ± 0.37% to 1.43% ± 0.28%; Bax protein expression rate From 1.34% ± 0.47% to 0.68% ± 0.30%. Conclusions rHu-EPO can inhibit cardiomyocyte apoptosis and preserve cardiac function, probably through down-regulating Bax expression and up-regulating bcl-2 expression.