激活Notch信号的骨髓间充质干细胞移植促心肌梗死模型鼠血管新生研究

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,建模2周进行相应处理后,随机分为MI模型对照组（B组）、培养液移植对照组（C组）、激活Noth信号的BMSCs移植实验组（D组）、BMSCs移植对照组（E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A、B、C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）,且D组较E组更明显（P〈0.05）。结论激活Notch信号有促进心肌梗死区BMSCs向内皮细胞分化,并通过自分泌和旁分泌的方式增加缺血心肌VEGF的表达,由此促进缺血心肌中毛细血管新生。

Effects of Transplantation of Activation of Notch Signal of Bone Mesenchymal Stem Cells on vasa Sanguefera Neogenesis of Myocardium of Myocardial Infraction

Objective To study the effect and mechanism of transplantation of activated Notch signal of bone mesenchymal stem cells（BMSCs） on vasa sanguefera neogenesis of myocardium of myocardial infarction. Methods Sixty Wistar rat with deligation of anterior descending（LAD） coronary artery as a myocardial infarction（MI） model were randomly divided into BMSCs with AMI model group（group B） and culture medium transplantation control group（group C） and Notch signal activation transplantation group（group D）,BMSCs transplantation control group（group E）.Ten shamoperation animals were set as the control group.Four weeks later,the expression of VEGF protein and capillary density in the ischemic myocardium were determined.At the same time,the differentiated myofibers from BMSCs in the in-farcted site were observed.Results The BMSCs were progressively differentiated into striated muscle fibers in the myocardial infarction site.Compared with that of group A,B and C,the expression of VEGF mRNA,VEGF protein and capillary density in the ischemic myocardium were markedly increased in group D and E（P〈0.01 ）.Capillary density in the BMSCs in group D was higher than that in the group E（P〈0.01）.Conclusion The BMSCs with Notch signal activation,after being implanted into the myocardial infarction site,not only show myocardial regeneration,but also show the ability to improve the expression of VEGF mRNA,protein and the vasa sanguefera neogenesis in the ischemic myocardium.