骨髓间充质干细胞心肌移植对大鼠心梗后血管新生和细胞因子分泌的作用

The Effect of Mesenchymal Stem Cells Transplantation on Angiogenesis and Secretion of Cytokines After Rat Myocardial Infarction

目的 探讨骨髓间充质干细胞心肌移植对大鼠心梗区血管新生和细胞因子VEGF、TGF的影响。方法 取大鼠骨髓间充质干细胞进行体外培养、增殖和标记 ,同时以液氮冷冻左室游离壁建立心梗模型。 4周后分别将 2× 10 6个细胞悬液或冷D -Hanks液注入心梗区数个不同部位。于移植后 1、2、4周依次获取心梗区标本 ,进行细胞形态学观察 ,毛细血管密度测定和RT -PCR检测细胞因子VEGF、TGF -βmRNA的表达。 结果 骨髓间充质干细胞于移植后 1、2、4周后均可存活并具有分化成熟倾向。移植后第 1、2及 4周心梗区单位面积 ( 0 1mm2 )毛细血管数实验组较对照组均明显增加 (P <0 0 1) ,但毛细血管数有随时间推移而逐步减少的趋势 (P <0 0 1)。VEGFmRNA术后第 1、2及 4周的表达水平实验组与对照组相比均增加 (P <0 0 1) ,且随着时间的推移其表达量两组均呈迅速降低的趋势 (P <0 0 1)。TGF -βmRNA在术后第 1、2及 4周的表达水平实验组与对照组相比均降低 ( P <0 0 1)。结论 骨髓间充质干细胞心梗区移植后可促进大鼠心梗后血管新生 ,并可使VEGF生成增加 ,TGF

Objective To investigate the effect of mesenchymal stem cells transplatation on angiogenesis and secretion of cytokines after rat myocardial infarction. Methods Harvested rat mesenchymal stem cells were cultured and labeled in vitro. And at the same time, myocardial infarct model was set up by liquid nitrogen cryoinjuring the left ventricular free wall. 4 weeks later, 2×10 6 mesenchymal stem cells or cold D-Hanks liquid were injected into several different points of infarcted area. At 1, 2 and 4 weeks after mesenchymal stem cells transplatation, specimens were acquired from infarcted area. Then cell morphology and capillary density were measured, and vascular endothelial growth factor(VEGF) and transforming growth factor β(TGF-β) expression levels were assayed by RT-PCR. Results Mesenchymal stem cells were alive at 1, 2 and 4 weeks after transplantation and had a trend toward differentiation and maturation in vivo. The number of capillary vessels in per infarcted area (0 1 mm 2) in experiment group increased compared with control group. And the number of capillary vessels in experimental group had a trend to decrease in experiment group(P<0 01), but had no obvious change in control group. The levels of VEGF mRNA expression at 1, 2, and 4 weeks obviously increased in experiment group compared with control group(P<0 01), but quickly decreased with time. And the levels of TGF-β mRNA expression in experimental group at 1, 2, and 4 weeks all obviously decreased compared with control group. Conclusion Mesenchymal stem cells transplantation can up-regulate the VEGF expression and down-regulate the TGF-β expression, which may accelerate angiogenesis in infarcted area after rat myocardial infarction.