大鼠神经干细胞脑内移植治疗脑出血的实验研究

Transplantation of NSCs into the Brain of Rats with Intracerebral Hemorrhage

目的:探讨大鼠神经干细胞(NSCs)脑内移植治疗脑出血(ICH)后血管内皮细胞生长因子(VEGF)、纤维粘连蛋白(FN)、层粘连蛋白(LN)的表达情况及其对神经回路重建的作用。方法:进行大鼠NSCs的体外培养、传代、鉴定及BrdU标记,制备大鼠ICH模型,随机分为ICH组、移植组、假手术组及对照组,移植组予标记的NSCs移植于ICH大鼠脑内。在各时间点观察各组大鼠神经功能缺损情况,并采用免疫组织化学方法检测各组脑血肿周围区及正常脑组织VEGF、FN、LN的表达,观察移植组BrdU的表达及分布。结果:移植组大鼠神经功能缺损恢复较快,其神经功能评分在ICH后7、14 d较ICH组低(P<0.05);移植组的VEGF、FN在ICH后7、14及30d和LN在ICH后7、14d的表达均高于ICH组、假手术组及对照组(P<0.01),移植组有BrdU阳性细胞存在并分布于血肿区及移植区周围。结论:体外培养的大鼠NSCs移植入ICH大鼠脑内后,可促进大鼠神经功能缺损恢复,移植后VEGF、FN、LN的表达增加为外源性NSCs的增殖、迁移和分化及神经回路重建提供了条件。

Objective： To research the expression of vascular endothelial growth factor （VEGF）, fibronection （FN） and laminin （LN） after transplantation of neural stem cells （NSCs） into the brain of rats with intracerebral hemorrhage （ICH） and to investigate the effect on neural circuit reestablishment. Methods：The NSCs obtained form rats were cultured in vitro, and then identified by immunocytochemistry and with Bromodeoxyuridine （BrdU）. The models of rats with ICH were established, and divided into ICH, transplantation, sham operation and control groups. In transplantation group, NSCs with marker were transplanted into the brain of the rats with ICH. At each time point, all the rats were evaluated. The expressions of VEGF, FN and LN in tissues about the hematoma （or impairment and transplantation） and in the normal tissue zone were examined by immunohistochemistry staining. Results： The neurological deficits in the transplantation group improved rapidly, when compared with the ICH group at days 7 and 14 （P〈0.05）. BrdU^＋ cells were seen in the zone around hematoma and the transplantation zone in the transplantation group. Conclusion： Transplantation of NSCs into brains of rats with ICH may enhance recovery of the impaired nervous tissues caused by bleeding in rats.