骨髓间充质干细胞移植改善缺氧缺血性脑损伤大鼠空间学习记忆的最佳时间

Optimal time window of rat mesenchymal stem cell transplantation for improving spatial learning of neonate rats with hypoxic ischemic brain damage

目的探讨大鼠骨髓间充质干细胞(rMSCs)移植治疗新生鼠缺氧缺血性脑损伤(HIBD)的最佳时间点。方法体外培养rMSCs传代至4～5代,同时建立新生鼠HIBD模型,分别在HIBD后2、24、72、144h进行腹腔注射移植,5周后行水迷宫行为学检测。结果水迷宫实验中,HIBD后2h移植组(A组)、HIBD后24h移植组(B组)、HIBD后72h移植组(C组)、HIBD后144h移植组(D组)、假手术组(E组)、HIBDPBS对照组(F组)逃避潜伏时间组间比较,E组及各移植组逃避潜伏时间均明显低于F组(P<0.05),A组低于B、C、D组(P<0.05),D组低于B组、C组(P<0.05)。各组平台象限泳距占总泳距的比例组间比较,E组及各移植组均明显高于F组(P<0.05),D组低于E组(P<0.05)、高于B组和C组(P<0.05)。结论 rMSCs移植可明显改善HIBD大鼠的空间学习记忆功能,在HIBD后2h进行移植效果较其他时间点好。

Objective To investigate an optimal time window of rat mesenchymal stem cell （rMSCs） transplantation for rats with hypoxic ischemic brain damage （HIBD）. Methods The animal model of newborn rat HIBD was established,rMSCs was cultured in vitro,and the passage 4-5 rMSCs were selected to transplant into the rats with HIBD by intraperitoneal injection at the 4 time points （after 2 h,24 h,72 h,144 h of HIBD）. 5 weeks later,behavior reactivity was evaluated with Morri water maze. Results In the place nevigation test of Morris water maze,the escape latent time （ELT） of the sham operated group （group E） and other HIBD groups treated with rMSCs transplantation was shorter than that of the HIBD model group treated with PBS （group F） （P0.05）; there was no significant difference between the model group treated with rMSCs transplantation after 2 h of HIBD （group A） and group E （P0.05）,but the ELT of group A and group E was shorter than that of other groups （P0.05）; the ELT of the model group treated with rMSCs transplantation after 144 h of HIBD （group D） was shorter than that of model group treated with rMSCs transplantation after 24 h of HIBD （group B） and the model group treated with rMSCs transplantation after 72 h of HIBD （group C） （P0.05）,there was no difference between group B and group C （P0.05）. In the spatial probe test of Morris water maze,the proportion of the quadrantal swimming distance in the platform quadrant of group E and other HIBD groups treated with rMSCs transplantation was longer than that of group F （P0.05）,there was no significant difference between group A and group E （P0.05）,group A and group D （P0.05）; the proportion of the quadrantal swimming distance in the platform quadrant of group D was shorter than that of group E （P0.05）,however,longer than that of group B and group C （P0.05）. Conclusion The capability of spatial learning of the rats with HIBD can be improved after treated with rMSCs transplantation,the optimal time point of transplantation was 2 h after HIBD in this study.