人骨髓基质细胞移植治疗脑出血的实验研究

Application of intravenous administration of human bone marrow stromal cells in treatment of intracerebral hemorrhage in rats

目的 探索人骨髓基质细胞（ hBMSCs）静脉移植治疗脑出血的实验效果及其可能机制.方法 选用成年雄性Wistar大鼠80只,随机分为对照组及3个移植不同数量（1×106/ml,3×106/ml,6×106/ml）细胞的治疗组.经尾静脉注射hBMSCs治疗大鼠脑出血.计算分析神经学缺陷程度分数、尾状核组织损失的百分率以及TUJ1 、BrdU、mAb1281、突触素免疫组化结果.结果 脑出血后14d,3个治疗组的神经功能明显改善（P＜0.05）；尾状核组织损失面积明显减小（P＜0.05）；TUJ1、BrdU、突触素的阳性细胞染色面积明显增加（P＜0.05）；mAb1281阳性染色细胞大量出现在脑出血区（P＜0.05）.结论 经尾静脉移植hBMSCs,能明显改善脑出血大鼠的神经功能,这与脑出血区尾状核组织损失较小、神经元及神经突触再生有关.

Objective To investigate the therapeutic effects and possible mechanism of intravenous administration of human bone marrow stromal cells （hBMSCs） in the treatment of intracerebral hemorrhage in rats.Methods Eighty adult male Wistar rats were randomly divided into four experimental groups,which consisted of 3 treatment groups and 1 control group.The intracerebral hemorrhage （ICH） in rats was treated by injecting hBMSCs into the rats＇ tail veins.The neurological function was evaluated using NSS.The percentage of striatal tissue loss in one section was calculated using an image analysis system.All rats were immunohistochemically analyzed using TUJ1,mAb1281,BrdU and Synaptophysin.Statistical evaluation of functional scores,area of ICH - related tissue damage,and histochemical results were performed using independent Student t - test- Results There was apparent difference between the control group and any of the treatment groups in the results of NSS 14 day after ICH（ P 〈0.05）.There was virtually difference between the control group and any of the treatment groups in the area of striatal tissue loss as a percentage of the normal hemisphere 2 weeks after ICH（ P 〈0.05）.The BrdU,Synaptophysin and TUJ1 histochemical staining data suggested that there was significant increase in the positive -staining cells in the region of ICH for all treatment groups compared with the controls （ P 〈 0.05 ）.Labeling of mAb1281 was seen in the treated animals in the region of ICH（ P 〈0.05）,verifying that the injected hBMSCs did reach the site of injured brain preferentially compared with the contralateral hemisphere.Conclusions Intravenous injection of hBMSCs at doses of 1,3 and 6 million cells 14 day after experimental ICH improves neurological function,and is associated with reduced striatal tissue loss,increased local presence of hBMSCs at the site of hemorrhage,significant increases in mitotic activity,immature neurons,synaptogenesis.