PD模型中GDNF与星形胶质细胞对黑质DA能神经元的影响

Effect of astrocytes and GDNF on dopamine neurons in substantia nigra of PD model rats

目的探讨星形胶质细胞和胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)在帕金森病(Parkinson's disease,PD)中对多巴胺(dopamine neurons,DA)能神经元损伤的影响。方法成年大鼠右侧前脑侧束注射6羟多巴胺(6-OHDA)制备PD模型。PD模型右侧黑质内注射GDNF,于注射后第6周采用免疫组织化学方法观察星形胶质细胞神经纤维酸性蛋白(glial fibrillary acidic protein,GFAP)以及多巴胺能神经元酪氨酸羟化酶(tyrosine hydroxylasa,TH)的变化。结果模型组、PBS和GDNF组注射侧与非注射侧星形胶质细胞相比,均发现GFAP阳性细胞明显增多,DA能神经元数量明显减少(P<0.05)。GDNF组与模型组相比,发现GFAP阳性细胞明显增多,同时残存的DA能神经元数量有所增加(P<0.05)。结论黑质内注射GDNF可能通过激活的星形胶质细胞保护PD大鼠模型黑质DA能神经元。

Objective To investigate the effect of astrocytes and GDNF on the degeneration of dopamine neurons in substantia nigra（SN） of PD model rats. Methods The PD rats were prepared by steriotaxic injection of 6-OHDA into right medial forebrain ＇ bundle, with the qualified models screened by behavioral analysis. Having survived for 7 days after the injection of 6-OHDA, GDNF was injected into the ipsilateral subatantia nigra（SN）. At the 6th week after GDNF injection, glial fibrillary acidic protein（GFAP） of astroglia and tyrosine hydroxylase（TH） of dopamine neurons were observed by immunohistochemical staining. Results In the injection side of model, PBS and GDNF group, the number of GFAP-positive astrocytes obviously increased and the number of dopamine neurons obviously decreased. There was a significant deviation between the injection side and the non-injection side（P〈0.05）. Compared with model group, the number of GFAP-positive astrocytes obviously increased and the survival of dopamine neurons accrued （P〈0.05）. Conclusion The intranigral infusion of GDNF can activate astrocytes to protect the DA neurons in Parkinson＇s disease model rats.