血红素氧合酶1提高骨髓间充质干细胞在梗死后心脏的存活

背景：移植骨髓间充质干细胞(bone mesenchymal stem cells，BMSCs)修复梗死后心功能受到围移植期移植细胞大量死亡的限制。因此寻找一种保护因子对移植细胞提供保护至关重要。 目的：观察血红素氧合酶1(heme oxygenase，HO-1)对BMSCs在梗死后心脏生存的影响。 方法：体外分离扩增培养大鼠BMSCs，Adv-hHO-1、Adv-GFP分别转染，移植前DAPI标记。结扎左前降支1 h后，分别将DAPI-hHO-1-BMSCs、DAPI-GFP-BMSCs多点注射到大鼠心脏梗死区周边，对照组注射等量PBS。 结果与结论：Adv-hHO-1转染BMSCs后获稳定表达。仅hHO-1-BMSCs组稳定表达hHO-1 mRNA；hHO-1-BMSCs组血管内皮生长因子、碱性成纤维细胞生长因子、肝细胞生长因子表达均高于其他两组(P < 0.01)；存活BMSCs数量在第3，7天均明显高于GFP-BMSCs组(P < 0.05)；大鼠心功能各项参数明显优于其他两组(P < 0.01)。移植4周后，HO-1-BMSCs组梗死区周边毛细血管密度明显高于GFP-BMSCs组和对照组(P < 0.01)，且胶原蛋白沉积减少，心室壁变厚，梗死面积较其他两组明显缩小(P < 0.01)。提示HO-1提高移植到梗死心脏BMSCs的存活，HO-1协同BMSCs抑制心室重构，改善心功能。

Human heme oxygenase-1 improves the survival of bone marrow mesenchymal stem cells in ischemic heart

BACKGROUND:Cardiac function is limited by the great amount of dead transplanted cells following myocardial infarction (AMI) treatment with bone marrow mesenchymal stem cells (BMSCs) transplantation. OBJECTIVE:To investigate the effects of human heme oxygenase-1 (HO-1) on the survival of BMSCs in the heart after AMI. METHODS:BMSCs were isolated, cultured and proliferated in vitro, transfected with Adv-hHO-1 and Adv-GFP, and then labeled with DAPI before transplantation. At 1 hour after left coronary artery ligation, DAPI-HO-1-BMSCs or DAPI-GFP-BMSCs were directly injected into the border of infracted cardiac region in rats. An equal volume of PBS was injected into the control group. RESULTS AND CONCLUSION:The expression of hHO-1 mRNA, vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor in the border of infracted cardiac region treated with HO-1-BMSCs were higher than those treated with GFP-BMSCs and PBS (P < 0.01), and the number of BMSCs and capillary vessels in AMI heart treated with HO-1-BMSCs was significantly higher than those treated with GFP-BMSCs and PBS (P < 0.05, P < 0.01). The heart function and remolding of the hearts treated with HO-1-BMSCs was better than those treated with GFP-BMSCs and PBS (P < 0.01). The infarct area in the HO-1-BMSCs group was also smaller than that in the GFP-BMSCs and PBS groups (P < 0.01). HO-1 enhances the survival of BMSCs in the AMI heart, which cooperates with BMSCs to inhibit ventricular remodeling and improve the cardiac function.