间充质干细胞移植对缺氧缺血性脑损伤新生大鼠脑内胶质细胞源性神经营养因子含量的影响

The effects of transplantation of mesenchymal stem cells on GDNF in neonatal rats with hypoxic-ischemic brain damage

目的观察间充质干细胞(MSCs)移植对缺氧缺血性脑损伤(HIBD)新生大鼠脑内胶质细胞源性神经营养因子(GDNF)含量的影响,初步探讨MSCs移植治疗新生大鼠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2.5 h制作HIBD模型。24 h后,MSCs移植组(n=20)经尾静脉注射1×106个/mL MSCs,PBS对照组(n=20)尾静脉注射PBS(0.01 mL/g),HIBD手术组(n=20)和正常对照组(n=20)不作注射。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、14 d各组大鼠神经功能及脑内GDNF含量。结果 MSCs移植后7、14 d,MSCs移植组的神经功能损害评分明显低于PBS对照组和HIBD手术组(P<0.05)。造模后,所有HIBD大鼠的GDNF含量均较正常对照组明显升高(P<0.05)。与PBS对照组和HIBD手术组比较,MSCs移植组在各个时间点的GDNF含量升高更为明显(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GDNF的合成和分泌,从而发挥神经保护和修复作用。

Objective To observe the change of glial cell line - derived neurotrophic factors （GDNF） in neonaral rats with hypoxic -ischemic brain damage （HIBD） after transplantation of mesenehymal stem ceils （MSCs）, and to study the mechanism of neural function recovery by MSCs transplantation in neonatal rats with HIBD. Methods MSCs from marrows of SD rats were isolated and cultured. Neonatal rats of 7 days of age were subjected to ischemia and hypoxia injury by ligation of left carotid artery. MSCs and PBS were administrated into MSCs transplantation group （ n = 20） and PBS control group （ n = 20 ）, respectively, 24 hours after surgery ; while no treatment was given in normal group （ n = 20） and HIBD operation group （n = 20）. Modified neurological severity score （mNSS） was assessed in all rats at 1, 3, 7 and 14 day. Meanwhile, GDNF was quantified by ELISA. Results Significantly lower mNSS was revealed in MSCs transplantation group than those in PBS control group and HIBD operation group at day 7 and 14 （ P 〈 O. 05 ）. Significant up - regulation of GDNF was observed in rats with HIBD comparing with that in normal group （ P 〈 0. 05 ）, while it was more prominent in MSCs group than those in PBS control group and HIBD operation group （ P 〈 0. 05 ）. Conclusion MSCs can alleviate neural deficits of neonatal rats with HIBD, probably via up - regulation of GDNF, which protects and repairs the neural system.