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目的促红细胞生成素(EPO)通过磷酸酰肌醇-3-激酶/蛋白激酶 B(PI3-K/Akt)途径诱导血管生成和抑制细胞凋亡。骨髓间充质干细胞(MSC)移植可以改善心肌缺血后心脏灌注和提高心功能。本研究探讨 EPO 能否增加 MSC 移植效果。方法将32只 Wistar 大鼠随机分为心肌梗死(MI)组、EPO 组、骨髓间充质干细胞移植组(MSC 组)和联合治疗组(MSC-EPO 组),永久结扎左冠状动脉前降支制备心肌梗死模型。通过局部注射的方法将培养的大鼠自体 MSC 移植入梗死区,EPO组及 MSC-EPO 组围手术期每天腹腔注射 EPO(3000 U/kg),共3天,14天后再连续注射3天,术后2天及21天检查二维超声心动图。术后21天用 Western blot 和免疫组化检测评价治疗效果。结果术后21天 MI 组心功能较术后2天明显恶化,而其余三组明显改善,尤以联合治疗组改善最为明显。术后21天,MSC-EPO 组心肌梗死面积(20.7%±2.3%)明显小于 MSC 组(24.0%±2.3%)、EPO 组(26.0%±0.9%)以及 MI 组(28.1%±1.5%)(均P<0.05);MSC-EPO 组毛细血管密度[(12.95±2.11)/视野]明显高于 MSC 组[(10.78±0.99)/视野]、EPO 组[(10.43±1.52)/视野]以及 MI 组[(6.31±0.69)/视野](均P<0.05);Bcl-2明显上调而 Bax 明显下调;磷酸化 Akt 与总 Akt 比值MSC-EPO 组(0.36)高于 MSC 组(0.32)、EPO 组(0.31)以及 MI 组(0.28)(均P<0.05),MSC 组、EPO组与 MI 组比较差异也有统计学意义(均P<0.05)。结论 MSC 移植和 EPO 注射均可改善心肌梗死后心功能。EPO 通过 PI3-K/Akt 途径增加 MSC 移植的治疗作用。
Objective Erythropoietin (EPO) induces angiogenesis and inhibits apoptosis through the phosphoinositide-3-kinase / protein kinase B (PI3-K / Akt) pathway. Bone marrow mesenchymal stem cells (MSCs) transplantation can improve cardiac perfusion and improve cardiac function after myocardial ischemia. This study explored whether EPO can increase MSC transplantation. Methods Thirty-two Wistar rats were randomly divided into myocardial infarction (MI) group, EPO group, bone marrow mesenchymal stem cell transplantation group (MSC group) and combination therapy group (MSC-EPO group), permanent ligation of left anterior descending coronary artery Preparation of myocardial infarction model. The cultured rats were transplanted into the infarcted area by local injection. EPO group and MSC-EPO group were intraperitoneally injected with EPO (3000 U / kg) per day for 3 days and then injected continuously for 3 days after 14 days. Two-dimensional echocardiography was examined 2 days and 21 days after surgery. 21 days after surgery with Western blot and immunohistochemistry to evaluate the treatment effect. Results The cardiac function of MI group was significantly worse than that of the 2nd day after operation on the 21st day after operation, while the other three groups were significantly improved, especially in the combination therapy group. At 21 days after operation, the myocardial infarct size (20.7% ± 2.3%) in MSC-EPO group was significantly lower than that in MSC group (24.0% ± 2.3%), EPO group (26.0% ± 0.9%) and MI group (28.1% ± 1.5% (12.95 ± 2.11) / visual field] in MSC-EPO group was significantly higher than that in MSC group [(10.78 ± 0.99) / visual field] and EPO group [(10.43 ± 1.52) / visual field] EPO group (0.36) was significantly higher than that of MSC group (0.32) in MI group [(6.31 ± 0.69) / field of vision] (all P <0.05); Bcl-2 was significantly increased and Bax was significantly decreased; EPO group (0.31) and MI group (0.28) (all P <0.05). There was also significant difference between MSC group, EPO group and MI group (all P <0.05). Conclusion Both MSC transplantation and EPO injection can improve cardiac function after myocardial infarction. EPO increases the therapeutic effect of MSC transplantation via the PI3-K / Akt pathway.