激活Notch信号的骨髓间充质干细胞心肌移植促进血管新生

摘要

目的 探讨干预Notch信号骨髓间充质干细胞(BMSCs)移植对心肌梗死(MI)大鼠心肌的治疗性血管新生作用及其机制.方法 60只Wistar大鼠经结扎冠状动脉前降支建立MI模型后2周进行相应处理后,随机分为激活Noth信号的BMSCs移植实验组(D组)、BMSCs移植对照组(E组)、培养液移植对照组(C组)、MI模型对照组(B组),每组15只;另选取10只为假手术对照组(A组).4周后观察细胞生长及增殖情况,测定缺血心肌中血管内皮细胞生长因子(VEGF)蛋白的表达及缺血区心肌毛细血管密度的改变.结果 BMSCs在梗死区中可增殖分化为内皮细胞.与B组、C组及A组相比,D组、E组缺血心肌中VEGF蛋白的表达增多及毛细血管密度均明显增高(P<0.01),D组较E组更明显(P<0.05).结论 Notch信号促进心肌梗死区BMSCs向内皮细胞分化,促进缺血心肌中毛细血管新生.%Objective To investigate the effect and mechanism of transplantation of Notch signal-activated bone mesenchymal stem cells(BMSCs) into myocardium after myocardial infarction (MI) to promote vasa sanguinea neogenesis. Methods MI model was established in 60 Wist ar rats by ligation of left anterior descending(LAD), which were randomly divided into groups of D(with Notch signal-activated BMSCs transplantation), E ( BMSCs transplantation control), C ( culture medium transplantation control) and B(MI model control) with 15 rats each. Another 10 rats were taken as sham operation group(A). Four weeks after injection, the expression of VEGF and capillary density in theischemic myocardium were determined. Results TheBMSCs differentiated into endothelial cells in the MI site. Compared with groups of A, B and C, the expression of VEGF protein and capillary density in the ischemic myocardium were markedly increased in groups of D and E(P＜0. 01). which in group D were higher than those in group E(P＜0. 05). Conclusion After being implanted into the MI site, the BMSCs with Notch signal activation may differentiate into endothelial cells and promote the myocardial regeneration.