胰岛素样生长因子-1预处理对大鼠骨髓间充质干细胞移植效率及心肌修复的影响

Effect of Insulin-Like Growth Factor-1 on Mesenchymal Stem Cell Transplantation and Myocardium Rebuilding in Myocardial Infarction Rats

目的：探讨胰岛素样生长因子-1（IGF-1）预处理对大鼠骨髓间充质干细胞（MSCs）移植效率及心肌修复的影响。方法：不同浓度的IGF-1（0、2．5、5、10ng／m1）以不同时间（4、12、24、48h）预处理MSCs，流式细胞术分析趋化因子受体4的表达。建立大鼠心肌梗死模型，尾静脉分别注射不含细胞的100斗l培养液（对照组），无预处理的MSCs（MSCs组）和含经IGF．1预处理的MSCs（IGF-1-MSCs组），每组8只大鼠。MSCs移植4周后分析血流动力学和心肌梗死面积，移植细胞的归巢情况，Ⅷ因子相关抗原的表达，心肌特异性蛋白肌钙蛋白T的表达。结果：流式细胞术昆示10ng／ml IGF-1预处理48h后MSCs趋化因子受体4的表达较0、2．5、5ng／mlIGF．1预处理48h后显著增高（P三0．01）。细胞移植4周后IGF-1-MSCs组较对照组和MSCs组左心室收缩末压和最大压力上升速率均显著增加（P〈0．01），左心室舒张末压均显著降低（P〈0．05），差异均有统计学意义。细胞移植4周后IGF-1-MSCs组较对照组和MSCs组左心室游离壁厚度、血管密度、肌钙蛋白T均显著增加（P〈0．05～0．01），心肌梗死面积、胶原容积分数均显著降低（P〈O．05～0．01），差异均有统计学意义。荧光阳性细胞IGF-1-MSCs组较对照组显著增加（P〈0．05），但较MSCs组差异无统计学意义（P〉0．05）。结论：IGF-1通过提高MSCs的归巢情况来提高细胞移植治疗心肌梗死的效果。

Objective ：To investigate the effect of insulin-like growth factor-1 （IGF-1）on mesenchymal stem cells （MSC）transplantation and myocardium rebuilding in myocardial infarction（ MI）rats. Methods ：In vitro ： MSC were pre-treated with IGF-1 at 0,2.5,5.0,10 ng/ml for 4,12,24 and 48 hours respectively. Chemo- kine receptor CXCR4 in MSC surface was measured with flow cytometry. In vivo ： MI model was established in rats and the experiment was divided into 3 groups. Control group, 100 Ixl DMEM basal medium was infused via the tail vein of rats,MSC group, 100 μl of 1 x 10^7 MSC was infused,and IGF-1-MSC group,100μl of 10ng/ml IGF-1 pre-treated MSC was infused, n =8 in each group and all rats were treated for 4 weeks. By the end of MSC transplantation, the left ventricular function, myocardial infarction size,the expression of cardiac-specific protein troponin T（TnT） ,and MSC adherence were examined respectively. Results ： Flow cytometry indicated that the best CXCR4 expression of MSC was obtained by 10ng IGF-1 pre-treatment for 48 hours （P 〈 0. 01 ）. After 4 weeks of transplantation, the left ventricular systolic end pressure increased （P 〈 0. 01 ）, and the left ventricular diastolic end pressure decreased （ P 〈 O. 05 ） in IGF-1-MSC group than that in Control group and in MSC group. TnT protein expression and the capillary density in peri-infracted area were enhanced, the collagen deposition and the infarct area wereattenuated in IGF-1-MSC group （ P 〈 0. 05 ）. Flow cytometry presented that positive MSC were significantly increased in IGF-1-MSC group than that in Control group（P 〈0.05）. Conclusion：IGF-1 improves the efficacy of MSC transplantation in MI rats, which might be via the enhancement of cell adherence in the infarcted heart.