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

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，初步探讨间充质干细胞移植治疗新生大鼠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2.5h制作HIBD模型。24h 后，MSCs移植组（n=20）经尾静脉注射1×106个MSCs，PBS对照组（n=20）尾静脉注射PBS（0.01ml /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(mNSS)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GDNF含量。结果 MSCs移植后7、14d，MSCs移植组的神经功能损害评分明显低于PBS对照组和HIE手术组（P<0.05）。制模后，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HIE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。

The Study on the Changes of GDNF in Neonatal Rats with Hypoxic-Ischemic Brain Damage after Transplantation of Mesenchemal Stem Cells

Objective To observe the changes of glial cell line derived neurotrophic factors(GDNF)in neonatal rats with hypoxic-ischemic brain damage(HIBD) after transplantation of Mesenchemal Stem Cells(MSCs),and to study the mechanism of recovering neural function by MSCs transplantation after HIBD in neonatal rats. Methods Isolated and cultured MSCs from marrows of SD rats.7-days-old neonatal rats were subjected to ischemia and hypoxia injury. 24h after that, MSCs or PBS was administrated into MSCs transplantation group(n=20) and PBS control group(n=20) respectively, while normal group(n=20) and HIBD operation group(n=20) didn’t take those. All of the rats took the modified Neurological Severity Score (mNSS) at 1,3, 7, 14d after transplantation of MSCs or PBS. Then detected the content of GDNF by ELISA. Results Results of mNSS of MSCs transplantation group was much lower than that of PBS control group and HIBD group 7,14d after MSCs transplantation(P<0.05).The content of GDNF in rats with HIBD was much higher than that of the normal group (P<0.05), and to compared with the PBS control group and HIBD operation group, it was the highest in the MSCs transplantation group(P<0.05).Conclusions MSCs can improve neural deficits of neoratal rats with HIBD, and increased the content of GDNF which protected and repaired the neural system.