Erythropoietin protects against doxorubicin-induced heart failure
Erythropoietin protects against doxorubicin-induced heart failure
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DOI：
10.1152/ajpheart.01096.2010
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发表时间：
2011-12-01
影响因子：
4.8
通讯作者：
Dhingra, Sanjiv
中科院分区：
文献类型：
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作者：
Ammar, Hania Ibrahim;Saba, Soliman;Dhingra, Sanjiv
Ammar HI、Saba S、Ammar RI、Elsayed LA、Ghaly WB、Dhingra S。促红细胞生成素可预防阿霉素诱导的心力衰竭。 Am J Physiol Heart Circ Physiol 301：H2413-H2421，2011。首次发表于 2011 年 10 月 7 日； doi:10.1152/ajpheart.01096.2010.-促红细胞生成素 (EPO) 已被证明具有心脏保护特性。本研究调查了 EPO 在预防阿霉素 [阿霉素 (AD)] 癌症治疗后心力衰竭中的作用。用盐水处理雄性Wistar大鼠（150+/-10g）（载体对照组）；使用 EPO，皮下注射 1,000 IU/kg 体重，每周 3 次，持续 4 周（EPO 组）；阿霉素，腹腔注射2.5 mg/kg体重，每周3次，持续2周（AD组）；以及阿霉素和 EPO（EPO-AD 组）。超声心动图测量表明 EPO-AD 治疗可防止 AD 引起的心功能下降。然后，在 Langendorff 灌注过程中，将每颗心脏暴露于缺血和再灌注。在左心室发展压、最大压力增加和心率压力乘积方面，EPO-AD 组缺血再灌注后的恢复百分比显着高于 AD 治疗组。 AD（5μM，24小时）暴露的分离心肌细胞的氧化应激水平显着较高； EPO（5 U/ml，持续 48 小时）治疗可防止这种情况发生。 EPO 治疗还减少了 AD 诱导的心肌细胞凋亡，这与 Bax 与 Bcl2 比率和 caspase-3 激活的降低有关。心肌组织 CD31 免疫染色显示，AD 治疗动物的毛细血管数量显着减少。 EPO-AD治疗恢复了毛细血管的数量。总之，EPO 治疗有效预防 AD 引起的心力衰竭。 EPO 的保护作用与心肌细胞氧化应激和细胞凋亡水平的降低以及心肌血管生成的改善有关。
Ammar HI, Saba S, Ammar RI, Elsayed LA, Ghaly WB, Dhingra S. Erythropoietin protects against doxorubicin-induced heart failure. Am J Physiol Heart Circ Physiol 301: H2413-H2421, 2011. First published October 7, 2011; doi:10.1152/ajpheart.01096.2010.-The hormone erythropoietin (EPO) has been demonstrated to have cardioprotective properties. The present study investigates the role of EPO to prevent heart failure following cancer treatment with doxorubicin [adriamycin (AD)]. Male Wistar rats (150 +/- 10 g) were treated with saline (vehicle control group); with EPO, subcutaneously at 1,000 IU/kg body wt, three times per week for 4 wk (EPO group); with adriamycin, intraperitoneally at 2.5 mg/kg body wt, three times per week for 2 wk (AD group); and with adriamycin and EPO (EPO-AD group). Echocardiographic measurements showed that EPO-AD treatment prevented the AD-induced decline in cardiac function. Each of the hearts was then exposed to ischemia and reperfusion during Langendorff perfusion. The percentage of recovery after ischemia-reperfusion was significantly greater in EPO-AD than the AD-treated group for left ventricular developed pressure, maximal increase in pressure, and rate pressure product. The level of oxidative stress was significantly higher in AD (5 mu M for 24 h)-exposed isolated cardiomyocytes; EPO (5 U/ml for 48 h) treatment prevented this. EPO treatment also decreased AD-induced cardiomyocyte apoptosis, which was associated with the decrease in the Bax-to-Bcl2 ratio and caspase-3 activation. Immunostaining of myocardial tissue for CD31 showed a significant decrease in the number of capillaries in AD-treated animals. EPO-AD treatment restored the number of capillaries. In conclusion, EPO treatment effectively prevented AD-induced heart failure. The protective effect of EPO was associated with a decreased level of oxidative stress and apoptosis in cardiomyocytes as well as improved myocardial angiogenesis.