骨髓间充质干细胞移植对大鼠脑缺血区血管新生及神经前体细胞增殖的影响

Effects of bone marrow mesenchymal stem cells transplantation on angiogenesis and neuronal progenitor proliferation in injured region of middle cerebral artery occlusion rats

目的:探讨骨髓间充质干细胞(MSC)移植促进大鼠脑缺血后神经功能恢复的可能机制。方法:用线栓法复制大鼠脑缺血再灌注动物模型,分缺血对照组和移植治疗组(经颈动脉移植体外培养异体MSC)。采用免疫组织化学染色及原位杂交技术观察缺血区脑组织的新生血管、细胞增殖及巢蛋白表达的变化。结果:(1)移植组比对照组缺血区皮层微血管密度(MVD)明显增高,血管内皮生长因子(VEGF)mRNA阳性信号明显增强。(2)缺血区顶叶皮层、尾壳核、室管膜、室管膜下区均可见大量Nestin阳性细胞及BrdU阳性细胞,各时间段移植组两种阳性细胞数均比对照组显著增多。结论:MSC可能通过改善缺血区血运及促进缺血区神经前体细胞再生达到修复缺血区损伤组织,从而改善脑缺血大鼠神经功能。

Objective： To explore the mechanisms of bone marrow mesenchymal stem cells （MSC） implantation on neurofunctional recovery following focal cerebral ischemia in rats. Methods： Forty healthy female rats were subjected to middle cerebral artery occlusion （MCAo） for 2 h by intraluminal vascular occlusion, and were divided into MSC transplantation group and cerebral ischemia control groups at random. 24 h after MCAo MSCs were administrated via carotid artery, lmmunohistochemistry and in situ hybridization methods were used to investigate the regeneration of microvessels and proliferation of neuronal progenitors in ischemic region. Results： The microvasculature density （MVD） and VEGF mRNA positive signals in the injured cortex of rats treated with MSC were significantly higher than those of the control groups. After MCAo, numerous nestin-positive cells and BMU-labelled cells were observed in the injured cortex of parietal lobe, caudate putamen, ependyma, subependymal zone. The nestin-positive cells in MSC transplanted group were significantly more than those of control group, and the same was true to BrdU positive cells. Conclusion： The results suggest that MSC transplantation can improve neurofunction in cerebral ischemic rats through promoting revascularization and proliferation of neuronal progenitors in the injured region.