间充质干细胞移植对缺氧缺血性脑损伤新生大鼠脑内碱性成纤维细胞生长因子含量的影响

Effect of mesenchymal stem cells transplant on cerebral content of basic fibroblast growth factor in neonatal rats with hypoxic-ischemic brain injury

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 mesenchymal stem cells （MSCs） transplanted into neonatal rats with hypoxic-ischemic brain damage （ HIBD）, in order to observe the changes of cerebral basic fibroblast growth factor （bFGF） and to explore the mechanism of MSCs transplantation for recovering neural function of neonatal rats with HIBD. Methods The MSCs were isolated from the bone marrow of SD rats and purified by in vitro culture. The left common carotid artery of SD rats was ligated and exposed under hypoxic condition for 2.5 hours to produce HIBD status. After 24 hours, 1 ×10^6 MSCs were injected through ratstail veins for the MSCs transplant group （n = 20）, phosphate buffered saline （PBS） were injected for transplant control group （n = 20）. Two other groups had no injections： the HIBD-model group （n = 20） and normal control group （n = 20）. All of the rats were scored by the modified neurological impairment score at 1, 3, 7, 14 days after the transplanting of MSCs or PBS. Cerebral bFGF levels were measured by the ELISA method. Results The nerve function impairment score of rats at 7 or 14 days after MSCs transplant （5.0 ±0.7, 4. 4 ± 1.1 ） were better than those in the PBS control group （6.8±1.5, 6.4±1.1） and HIBD- model group （7.0 ±1.0, 6.0±0.7）. All P values were less than 0. 05. The cerebral bFGF levels of MSCs transplant group at each time-point weresignificantly higher than the other three groups （P 〈 0. 05 ）. Conclusion MSCs transplants can improve the neurological function in neonatal rats with HIBD and promote the synthesis and secretion of cerebral bFGF to protect and repair the neural system.