骨髓间充质干细胞介导的血红素氧合酶-1促进大鼠心肌梗死后血管再生简

 目的 探讨骨髓间充质干细胞 (MSCs) 介导的血红素氧合酶-1 (HO-1) 对心肌梗死后心 脏血管再生及左心室功能的影响。方法 取大鼠骨髓，体外分离扩增培养 MSCs，HO-1 腺病毒转染。结扎左前降支 1 h 后，分别将 HO-1-MSCs、MSCs 多点注射到大鼠心肌梗死区周边，对照组注射等量 PBS。 结果 MSCs 介导的HO-1能在体外及体内获得稳定表达；HO-1-MSCs组促血管生长因子VEGF、FGF2的表达及毛细血管密度明显高于 MSCs 组和对照组 (P < 0.01)；但促血管再生的作用可被HO抑制剂阻断。HO-1-MSCs组心肌细胞凋亡及纤维化明显低于MSCs 组和对照组 (P < 0.01)；HO-1-MSCs组左室收缩功能各项指标明显优于其他两组(P < 0.01)。HO-1-MSCs组心室壁变厚，心室腔明显缩小。结论 MSCs介导的血红素氧合酶-1能促进心肌梗死后心脏血管再生，改善左心室功能。

HO-1 transduced by MSCs promotes angiogenesis in rat infracted myocardium

Objective: Heme oxygenase-1 (HO-1) is a stress-inducible enzyme with diverse cytoprotective effects, and is reported a role for angiogenesis rencently. We investigated whether HO-1 transduced by MSCs can induce angiogenic effects in infracted myocardium. Methods HO-1 was transfected into cultured MSCs using an adenoviral vector. 1×106 Ad-HO-1-transfected MSCs (HO-1-MSCs) or Ad-Null-transfected MSCs (Null-MSCs) or PBS was respectively injected into rat hearts 1 h intramyocardially after myocardial infarction. Results HO-1-MSCs was able to induce stable expression of HO-1 in Vitro and Vivo. The capillary density and expression of angiogenic growth factors,VEGF and FGF2, were significantly enhanced in HO-1-MSCs-treated hearts compared with Null-MSCs-treated and PBS-treated hearts. However, the angiogenic effects of HO-1 in HO-1-MSCs group could be abolished by treating the animals with HO inhibitor, zinc protoporphyrin. The myocardial apoptosis was marked reduced with significantly reduced fibrotic area in HO-1-MSCs-treated hearts; Furthermore, the cardiac function and remodeling were also significantly improved in HO-1-MSCs-treated hearts than in the other two groups. Conclusion HO-1 modification with MSCs reduces the apoptosis of myocardium and preserves cardiac function and remodeling, and that this is associated with siginficant angiogenesis.