骨髓细胞移植上调血管内皮生长因子及其受体的表达并改善缺血心脏功能

目的：通过骨髓细胞移植对心肌梗死大鼠模型血管内皮生长因子及其受体表达的影响，探讨骨髓细胞移植改善缺血心脏功能的可能机制。方法：利用左前降支冠状动脉结扎术制备大鼠心肌梗死模型，然后行异体骨髓细胞移植；分别于术后1d，3d，7d，14d和28d取材；利用免疫荧光和RT—PCR技术分析细胞移植对血管内皮生长因子(VEGF)及其受体(Flk一1)表达的影响和移植细胞的分化情况；通过免疫组化计算血管数量；应用血流动力学检测大鼠心脏功能在术后各时间点的变化。结果：VEGF和Flk-1在移植组动物的心肌梗死区残存细胞、梗死周边区细胞以及部分移植细胞内表达。移植组VEGF和Flk-1的mRNA表达明显高于对照组。分别于术后3d和14d达到高峰，以后逐渐减弱。术后7d，14d和28d移植组血管数量较同期对照组明显增加，移植组心脏功能较对照组明显改善。术后14d可在部分移植细胞中检测到心肌细胞或血管内皮细胞特异性蛋白的表达。结论：骨髓细胞移植通过上调移植细胞及受者内源性VEGF和Flk—1的表达，促进血管新生，进而改善缺血心脏功能。

Transplantation of bone marrow cells upregulated vascular endothelial growth factor and its receptor and improved ischemic myocardial function

Objective: To investigate the possible mechanisms of improving ischemic myocardial function by transplantation of bone marrow cells in a rat ischemic heart model. Methods: Myocardial infarction was induced in inbred Lewis rats by left anterior descending artery ligation. Bone marrow cells were injected into an ischemic zone (BMI group). On days 1, 3, 7, 14 and 28 post transplantation, the expressions of vascular endothelial growth factor (VEGF) and its receptor (Flk 1) and the differentiation of transplanted cells were determined by immunofluorescence and RT-PCR. The number of vessels was examined by immunohistochemistry. The cardiac function was evaluated by hemodynamics. Results: Immunofluorescence microscopy of hearts from BMI group revealed that expressions of VEGF and Flk 1 were promoted within cardiomyocytes in the infarction zone, the peri infarct zone and in some transplanted bone marrow cells. RT-PCR also showed that mRNA expression levels of VEGF and Flk 1 in BMI group were significantly higher than those of the control group, reached the highest level on days 3 and 14 post transplantation, and then gradually declined. On days 7,14 and 28, the vessel count showed the number of blood vessels in the BMI group was greater than that of the control group at the same time,and the cardiac function in the BMI group was improved more significantly than that of the control group. After day 14, the specific markers for myocardium or vascular endothelial cells were detected in the transplanted bone marrow cells. Conclusions: BMI improved the acute ischemic cardiac function by both upregulating the expressions of VEGF and Flk 1 in transplanted BMCs and recipient endogenous cardiomyocytes that enhanced angiogenesis.