骨髓干细胞动员对高龄大鼠缺血心脏功能的保护作用

Protective effect of mobilization of bone marrow stem cell on ischemic myocardial function in aged rat.

目的:了解从老年大鼠中动员出的骨髓干细胞归巢于梗死心肌和分化的能力,以及对缺血心脏功能的影响,并探讨其可能机制。方法:W istar大鼠分为3组:高龄心肌梗死+动员组、高龄心肌梗死组和青年心肌梗死+动员组。结扎大鼠左冠状动脉制作急性心肌梗死(AM I)模型,动员组大鼠用骨髓干细胞动员剂干细胞因子动员自体骨髓干细胞释放并归巢于心肌梗死灶,于建模后24 h、48 h和4周杀死各组大鼠,取出心脏,通过免疫组化、HE染色方法观察老年大鼠心肌梗死灶、边缘区和正常心肌组织CD34阳性细胞浸润及心肌再生的情况,应用流式细胞仪比较动员前后外周血中CD34阳性细胞数量的变化,并应用BL-420E生物机能实验系统检测老年大鼠心功能指标。结果:使用干细胞因子后,高龄动员组及青年动员组大鼠外周血中CD34细胞数量显著升高,两组大鼠心肌梗死灶均可见大量CD34细胞浸润;高龄动员组大鼠在制模4周时心功能指标显著比高龄心肌梗死组改善,而高龄动员组和青年动员组的心功能指标无显著差异,均显著改善。制模后24 h,高龄动员组大鼠和青年动员组大鼠心肌梗死程度轻,可见CD34阳性的幼稚心肌细胞样细胞,4周后瘢痕组织少,缺血心肌的基本结构得到保护。结论:在骨髓干细胞动员剂作用下,从老年大鼠个体中动员出的骨髓干细胞归巢梗死心肌能力仍得到增强,有较多干细胞向梗死灶迁移,并向心肌细胞等分化,保护缺血心肌基本结构,改善心功能。

AIM ：To investigate the ability of stem cell factor（SCF ）-mobihzed bone marrow stem cells homing to infarcted myocardium and its differentiation in aged rat, and the influence on heart function. METHODS ：Left anterior descending coronary arteries were ligated to produce acute myocardial infarction（ AMI） model in Wistar rats. Rats were divided into 3 groups： aged MI ＋ mobilized group, aged MI group and young MI ＋ mobihzed group. Bone marrow stem ceils were mobilized by SCF and home to the site of myocardial infarction. Hearts were harvested from 24 hours to 4 weeks after AMI modeling for histopathological examination. Immunohistochemisty, HE stain were used to detect infiltration of CD34^＋ cells and the regeneration of myocytes. The CD34^＋ cell number before and after mobilization was determined with flowcytometry. Four weeks after modeling heart function each group was measured by using the biofunction laboratory system （ BL-420E system ）. RESULTS ： The number of CD34^＋ cells increased significantly in peripheral blood after mobilization of stem ceils in aged and young MI ＋ mobilized group. There were a great number of monocytes infiltrating with CD34 expression by immunohistochemisty in myocardial infarcted zone in aged and young mobilized rats. Compared with aged MI group, heart function in aged MI ＋ mobilized group was improved significantly, but there were no marked differences between aged MI ＋ mobilized group and young MI ＋ mobilized group. 24 hours after modeling, a large amount of infiltrative monocytes and regenerative myocytes which were CD34 positive expression could be found in the infarction zones of the aged and young mobilized groups, while majority of the infiltrative inflammatory cells in aged MI group were neutrophils and there was less infiltrative cells and myocytes which were CD34 positive expression. 4 weeks after modeling, there were a plenty of scar in aged MI group, but not in aged and young MI ＋ mobilized group. CONCLUSION. In aged rat AMI model, ability of bone marrow stem cells homing to infarcted myocardium increases after mobilization. SCF can mobilize many bone marrow stem cells to home to infarcted zones and differentiate to cardiomyocyte-like cells. The heart function is remarkably improved by regeneration of mvoevtes and orotection of ischemic myocardial structure.