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目的:探讨动员急性心肌梗死大鼠骨髓干细胞归巢于梗死心肌后实现血管再生的能力。方法:实验选用10～12周龄的雄性Wistar(清洁级)大鼠60只,随机分为3组:急性心肌梗死+动员组、急性心肌梗死组及对照组,每组20只。结扎Wistar大鼠左冠状动脉制作心肌梗死模型,用骨髓干细胞动员剂粒细胞集落刺激因子动员自体骨髓干细胞释放并归巢于心肌梗死灶,于造模后24,48h和4周杀死大鼠,取出心脏,通过免疫组化方法观察心肌梗死灶、边缘区和正常心肌组织CD34阳性细胞、血管内皮生长因子及其受体的表达,以及VIII因子表达,并应用流式细胞术比较动员前后外周血中CD34阳性细胞数量的变化。结果:急性心肌梗死+动员组大鼠造模24h,4周后外周血CD34细胞数量分别为(0.919±0.187)%,(0.834±0.110)%,明显高于造模前犤(0.043±0.023)%犦及心肌梗死组大鼠造模24h,4周后犤(0.071±0.104)%,(0.062±0.296)%犦(t=2.697,2.354,2.492,2.195,P<0.05)。急性心肌梗死+动员组大鼠心肌梗死区可见CD34阳性细胞浸润;制模后4周,急性心肌梗死+动员组微血管新生数明显多于急性心肌梗死组和对照组(t=3.125,3.308,P<0.01)。急性心肌梗死+动员组大鼠梗死灶及周围组织中血管内皮生长因子及其受体的表达量均明显高于急性心肌梗死组及假手术组(t=2.099～3.398,P<0.05)。结论:骨髓干细胞动员的方法在大鼠急性心肌梗死模型中,能通过动员内皮干细胞归巢于梗死灶内,有效促进微血管形成;还通过上调血管内皮生长因子及其受体的表达,促进血管再生,促进缺血心脏功能恢复。
Objective: To investigate the ability of mobilizing bone marrow stem cells of rats with acute myocardial infarction to achieve angiogenesis after homing to infarcted myocardium. Methods: Sixty male Wistar rats of 10-12 weeks old were randomly divided into 3 groups: acute myocardial infarction + mobilization group, acute myocardial infarction group and control group, with 20 rats in each group. The model of myocardial infarction was established by ligation of the left coronary artery in Wistar rats. The bone marrow stem cell mobilized granulocyte colony-stimulating factor was used to mobilize autologous bone marrow stem cells to release and homing to myocardial infarction. Rats were sacrificed at 24, 48 and 4 weeks after modeling, The hearts were removed and the expression of CD34 positive cells, vascular endothelial growth factor and its receptor, and the expression of factor VIII were observed by immunohistochemistry in peripheral blood of myocardial infarction, marginal zone and normal myocardium. Flow cytometry was used to compare peripheral blood before and after mobilization In the number of CD34-positive cells. Results: The numbers of CD34 cells in peripheral blood were (0.919 ± 0.187)% and (0.834 ± 0.110)% in acute myocardial infarction + mobilization group at 24 h and 4 weeks respectively, which were significantly higher than those before modeling (43 0.043 ± 0.023) % 犦 and myocardial infarction rats 24h, 4 weeks after 犤 (0.071 ± 0.104)%, (0.062 ± 0.296)% 犦 (t = 2.697,2.354,2.492,2.195, P <0.05). Acute myocardial infarction + mobilization group showed infiltration of CD34 positive cells in myocardial infarction area. At 4 weeks after model establishment, the number of angiogenesis in acute myocardial infarction + mobilization group was more than that in acute myocardial infarction group and control group (t = 3.125,3.308, P <0.01). The expression of vascular endothelial growth factor and its receptor in the infarcted area and the surrounding tissues in acute myocardial infarction + mobilization group were significantly higher than those in acute myocardial infarction group and sham operation group (t = 2.099-3.398, P <0.05). CONCLUSION: The method of mobilizing bone marrow stem cells can promote the formation of microvessels by mobilizing endothelial stem cells into the infarct in rat model of acute myocardial infarction, and promote the angiogenesis by up-regulating the expression of vascular endothelial growth factor and its receptor , Promote the recovery of ischemic heart function.