粒细胞集落刺激因子骨髓干细胞动员治疗兔心肌梗死的实验研究
Effects of bone marrow stem cells mobilization with granulocyte-colony stimulating factor for the therapy of myocardial infarction in rabbits
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摘要: 目的: 探讨粒细胞集落刺激因子(G CSF)骨髓干细胞动员对兔心肌梗死的治疗作用。方法: 将20支兔采用结扎前降支的方法制作心肌梗死模型,随机分为动员组和对照组,动员组(n=10)心梗后3h开始皮下注射G CSF30μg·kg 1·d 1,对照组(n=10)皮下注射等量生理盐水,连续使用5d。采用超声心动图(UCG)检查及血液动力学测定了解心脏功能变化,取心脏作免疫组织化学鉴定。结果: 心梗后5周,动员组左室射血分数(EF)与1周时相比明显增加,而且与对照组相比,EF值、左室舒张末压(LVEDP)、+dp/dtmax和dp/dtmax均有显著变化。在心肌梗死区发现有Brdu标记的阳性细胞,正常心肌组织则没有,动员组梗死区血管密度明显高于对照组,未发现有新生的平滑肌细胞及心肌细胞。结论: G- CSF骨髓干细胞动员治疗心肌梗死,能通过促进梗死区血管新生,明显改善心脏功能,可能为心肌梗死的治疗提供一种新的无创性手段。Abstract: Objective:To investigate the effects of bone marrow stem cells mobilization with granulocyte-colony stimulating factor(G-CSF) for the therapy of myocardial infarction in rabbits.Methods:The 20 rabbits were randomly divided 2 groups, myocardial infarction (MI) was induced by ligation of the left anterior descending artery. In mobilization group(M),G-CSF (30μg·kg -1·d -1) was injected subcutaneously 3 hours after MI and every 24 hours for 5 days,saline was injected in control group(C). Echocardiography, hemodynamic studies were performed for the evaluation of cardiac function, and histological study was performed. Results:LV ejection fraction(EF) of group M increased significantly 5 weeks after MI.EF,LV end-diastolic pressure(LVEDP), LV +dp/dtmax and -dp/dtmax of group M changed significantly compared with group C. Histological studies revealed that there were BrdU positive cells in the infarcted area of group M, and the vascular density of group M in the infarcted area was significantly greater in comparission with group C. No regeneration of smooth muscle cells and cardiomyocytes was found.Conclusions:Bone marrow stem cells mobilization with G-CSF significantly improves the cardiac function for the therapy of MI through vasculogenesis in the infarcted area.It may offer a new and non-invasive therapeutic strategy for MI.
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