骨髓干细胞动员疗法对心肌梗死大鼠心脏的促血管生成作用

The stimulate angiogenesis effect of mobilization of bone marrow stem cells on the hearts of myocardial infarction rats

目的探讨干细胞动员疗法对心肌梗死大鼠冠脉新生血管形成的影响及其作用机制。方法结扎Wistar大鼠左冠状动脉制作急性心肌梗死模型,应用粒细胞集落刺激因子动员自体骨髓干细胞释放并归巢于缺血心肌,建模后第24h、48 h和4周时处死大鼠,取出心脏,HE染色检测梗死面积,免疫组化方法观察心肌梗死灶、边缘区和正常心肌组织CD34+细胞、血管内皮生长因子(VEGF)及其受体(Flk-1)的表达以及Ⅷ因子表达。结果使用干细胞动员剂后,动员组大鼠心肌梗死区可见CD34+细胞浸润,心肌梗死面积明显减小,梗死灶及周围组织中微血管密度、VEGF及其受体的表达量均明显高于AMI组及假手术对照组。结论骨髓干细胞动员疗法在大鼠AMI模型中,通过动员骨髓干细胞归巢于梗死灶内,有效促进微血管形成;通过上调VEGF和VEGF受体Flk-1的表达,促进血管再生,促进缺血心脏功能恢复。

Objective To investigate the stimulate angiogenesis effect and mechanism of mobilization of bone marrow stem cells on coronary collateral development in the hearts of experimental myocardial infarction rats. Methods I.eft anterior descending coronary arteries were ligated to produce acute myocardial infarction（AMI） model in Wistar rats. Bone marrow stem cells were mobilized by G--CSF and home to the site of myocardial infarction. Hearts were harvested in the 24 th hour, 2nd and 4th week after AMI modeling for histopathological examination. Immunohistochemisty were used to detect infiltration of CD34^＋ cells and the expression of VEGF and its receptors（Flk-1）, Ⅷ factor in the part of ischemia. And infarct area were measured. Results Infarct area in mobilized group was obviously less than in AMI group. There were a great number of monocytes infiltrating with CD34 expression by immunohistochemisty in myocardial infracted zone in mobilized rats. Capillary density in mobilized group was greater than those of AMI and sham--operated groups. Expression of VEGF and Flk-1 was found in all group, but in mobilized group the expression of VEGF and Flk-- 1 enhanced obviously. Conclusion In the AMI model of rat, mobilization of bone marrow stem cells can increase the capillary density by mobilize bone marrow stem cells, and improve the acute ischemic cardiac function by upregulating the expressions of VEGF, Flk--1 and enhance angiogenesis.