体外长期培养的人神经干细胞对大鼠帕金森病模型的药效初探

Studies on pharmacodynamics of human neural stem cells which long-term cultured in vitro by the Parkinson's model rats

目的初步探讨体外长期连续培养的人神经干细胞(hNSCs)对大鼠帕金森病(PD)模型的药效。方法采用6-羟基多巴胺(6-OHDA)注射大鼠脑内黑质体部位,毁损黑质多巴胺能神经元建立PD大鼠模型。成模大鼠随机分为对照组、NSC混合、NSC高剂量、NSC低剂量四组,行脑内同侧纹状体部位移植h NSCs。行为学实验观察治疗效果,免疫荧光染色鉴定植入纹状体的hNSCs存活和分化情况。结果细胞移植后观测和检查:(1)NSC高剂量组在移植3个月后,大鼠的单侧旋转症状与移植前比较有显著的改善(P<0.05);NSC低剂量组大鼠旋转症状也有改善,但与移植前比较无显著性差异(P>0.05);NSC混合组大鼠旋转症状明显改善,与对照组比较有显著性差异(P<0.05)。(2)6-OHDA能明显损伤大鼠脑内黑质部位,使其神经元数量减少;神经干细胞纹状体部位移植后可见移植的干细胞分化为神经元。结论 PD模型大鼠纹状体部位移植的hNSCs可分化为神经元,且对PD模型大鼠旋转症状有明显的改善。

Objective Human neural stem cells(hNSCs)were cultured in vitro for a long time,and to investigate the efficacy of Parkinson's disease(PD)model rats.Methods The PD rat model was established by injecting 6-OHDA into substantia nigra.PD model rats were equally randomized into four groups:control group,NSC mixed,NSC high dose and NSC low dose.hNSCs were transplanted into the ipsilateral striatum.The effect of treatment was observed by behavioral experiments,and hNSCs in brain were detected by immunofluorescence staining.Results 3 months after cell transplantation,the rotation behavior of NSC high dose group was significantly improved as compared to that of before transplantation(P<0.05).NSC low dose group was improved too,but there was no significant difference(P>0.05)compared to the state before transplantation.NSC mixed group was significantly improved as compared with the control group(P<0.05).The substantia was damaged by 6-OHDA and the neurons were decreased.Neural stem cells could be induced differentiating to DA neurons in brain of PD rats.Conclusion After transplantation by striatum part,they can be differentiated into neurons,and the rotation behavior of PD model rats is significantly improved.