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目的探讨间充质干细胞(MSCs)移植治疗新生大鼠缺氧缺血性脑损伤(HIBD)的机制。方法体外分离培养4～6周龄SD大鼠骨髓MSCs。采用新生7日龄SD大鼠结扎左颈总动脉后低氧暴露2.5h制作HIBD模型。建模24h后,MSCs移植组(n=20)经尾静脉注射MSCs1×106个,磷酸盐缓冲液(PBS)对照组(n=20)尾静脉注射PBS0.01ml/g,HIBD组(n=20)和正常对照组(n=20)不注射。采用大鼠改良神经功能损害评分及ELISA法分别检测移植后1、3、7、14d各组大鼠神经功能及脑内碱性成纤维细胞生长因子(bFGF)含量。结果 MSCs移植后7、14d,移植组神经功能损害评分[(5.0±0.7)分,(4.4±1.1)分]均较PBS组[(6.8±1.5)分,(6.4±1.1)分]和HIBD组[(7.0±1.0)分,(6.0±0.7)分]低(P均<0.05)。各时间点MSCs移植组大鼠脑内bFGF含量明显高于其余3组(P<0.05)。结论 MSCs移植可改善HIBD新生大鼠的神经功能,促进脑内bFGF的合成和分泌,从而发挥神经保护和修复作用。
Objective To investigate the mechanism of mesenchymal stem cells (MSCs) transplantation for neonatal hypoxic-ischemic brain damage (HIBD). Methods Bone marrow MSCs from 4 to 6 weeks old were isolated and cultured in vitro. HIBD model was made by neonatal 7-day-old SD rats ligation of the left common carotid artery and exposure to hypoxia for 2.5 hours. After modeling for 24 h, MSCs transplantation group (n = 20) was injected with 1 × 106 MSCs through the tail vein and PBS (PBS = 0.01) into the caudal vein of mice in PBS group (n = 20) 20) and normal control group (n = 20) were not injected. The neurological function and the content of basic fibroblast growth factor (bFGF) in rats of each group were detected by modified neurological impairment score and ELISA method at 1, 3, 7 and 14 days after transplantation. Results Compared with PBS group [(6.8 ± 1.5) points, (6.4 ± 1.1) points] and HIBD (P <0.05), the scores of neurological dysfunction in transplantation group were significantly higher than those in PBS group at 7 and 14 days after MSCs transplantation (5.0 ± 0.7 and 4.4 ± 1.1) Group [(7.0 ± 1.0) points, (6.0 ± 0.7) points] low (all P <0.05). At each time point, the content of bFGF in the brain of MSCs transplantation group was significantly higher than the other three groups (P <0.05). Conclusion Transplantation of MSCs can improve the neurological function, promote the synthesis and secretion of bFGF in neonatal rats with HIBD, and thus play a neuroprotective and repair role.