转染肝细胞生长因子的骨髓间质细胞治疗大鼠缺血性脑卒中

目的探讨转染肝细胞生长因子（HGF）的骨髓间质细胞（MSCs）治疗大鼠脑缺血的效果。方法制备大鼠一过性大脑中动脉缺血（MCAO）模型。MCAO后24h分别将磷酸盐溶液（PBS）、MSCs和转染HGF的MSCs（MSC—HGF）通过立体定向技术植人缺血脑组织。通过改良神经功能严重性评分（mNSS）评价神经功能，应用免疫组织化学染色分析脑组织HGF表达、缺血脑组织边缘带细胞凋亡及存活神经元。结果治疗后2周，MSC—HGF组mNSS明显低于PBS组和EMCs组（P〈0.05）。治疗后第1天MSC—HGF组病变脑组织中HGF蛋白表达明显高于PBS组和EMCs组（P〈0．05）。治疗后1周，与PBS组和EMCs组相比，MSC—HGF组在梗死边缘带凋亡细胞的百分比明显减少（P〈0．05），存活神经元的百分比明显增加（P〈0.05）。结论转染HGF的MSCs治疗缺血性脑卒中具有抗细胞凋亡、神经保护作用。

Effect of transplantation of bone marrow stromal cells transfected with hepatocyte growth factor into ischemic cerebral region on ischemic stroke in rats

Objective To explore the effect of transplantation of bone marrow stromal cells （MSCs） transfected with hepatocyte growth factor （HGF） on the neurological function after the brain infarction in rats. Methods The models of the temporal cerebral ischemia were made by transient middle cerebral artery occlusion （MACO） in 45 rats, who were divided into 3 groups of 15 animals each including phosphate-buffered saline, MSCs alone, and HGF-transferred MSCs （MSC-HGF） treatment groups. All the reagents were used by stereotactic respective transplantation into the ischemic cerebral regions of animals in 3 group 24 hours after MCAO. The curative effects were compared among the groups through detecting the neurological function recovery by the behavioral test and the immunohistochemical determination of HGF expression and analysis of the apoptotic neurons in the edges of the ischemic cerebral regions. Results Behavioral tests showed significant improvement of neurological function in MSC-HGF group compared with the other groups 2 weeks after the treatment. Immunohistochemical analysis revealed abundant expression of HGF protein in the ischemic cerebral region of the MSC-HGF group compared to other groups 1 day after the treatment, and it lasted for at least 2 weeks. The percentage of apoptosis positive cells in the ischemic boundary zone （IBZ） was significantly decreased while that of remaining neurons in the cortex of the IBZ was significantly increased in the MSC-HGF group compared to the other groups. Conclusions The neurological function may be improved by HGF-MSCs treatment in the rats with ischemic stroke. The improvement of the neurological function may be related to HGF-MSCs anti-apoptosis and neuroprotective functions.