G-CSF对帕金森病小鼠运动能力和黑质纹状体神经元的影响

Effects of granulocyte colony-stimulating factor on nigrostriatal neurons in the mouse model of Parkinson's disease

目的:探讨粒细胞集落刺激因子(G-CSF)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致小鼠帕金森病(PD)模型中脑黑质致密部(SNpc)及纹状体(STR)多巴胺(DA)能神经元的影响。方法:正常健康雄性C57BL/6J小鼠随机分为对照组、MPTP组及MPTP+G-CSF组,采用腹腔注射MPTP法制作小鼠PD模型,MPTP+G-CSF组于最后一次MPTP注射后再腹腔注射G-CSF。爬杆实验观察小鼠的行为学改变;尼氏染色技术观察各组小鼠黑质致密部神经元数量及形态学变化;免疫组织化学法检测酪氨酸羟化酶(TH)在各组小鼠中脑黑质致密部及纹状体的表达; Western Blot法检测各组小鼠中脑TH蛋白的表达量。结果:与对照组相比,MPTP组小鼠较对照组爬杆用时显著延长(P <0. 05),尼氏染色显示黑质致密部神经元数量显著减少(P <0. 05),黑质致密部、纹状体TH表达量显著减少(P <0. 05); MPTP+G-CSF组较MPTP组爬杆用时显著缩短(P <0. 05),神经元丢失减少(P <0. 05),神经元形态较完整;与MPTP组比较,MPTP+G-CSF组黑质致密部、纹状体TH表达水平显著增高(P <0. 05)。结论:G-CSF能够改善PD小鼠运动功能,减少黑质致密部多巴胺能神经元丢失,增加TH表达水平。

Objective:To observe the effects of granulocyte colony stimulating factor(G-CSF)on the dopaminergic neurons(DA)of the substantia nigra pars compacta(SNpc)and striatum(STR)in the mouse Parkinson’s disease(PD)model of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Methods:The normal healthy male C57BL/6J mice were randomly divided into the saline control group,the MPTP-exposed group and the MPTP-exposed group followed by G-CSF treatment.The mice of PD model were intraperitoneally injected with MPTP,and the MPTP+G-CSF group was injected with G-CSF after the final MPTP injection.The behavioral changes of mice were observed by Pole Test.Staining of Nissl was then used to observe the number and morphological changes of neurons in SNpc in each group.Additionally,the expression of tyrosine hydroxylase(TH)in SNpc and STR of mice in each group was detected by immunohistochemistry,and the expression of TH protein in the midbrain of mice in each group was detected by Western Blot.Results:Compared with the saline control group,the time to reach the floor in group MPTP were significantly decreased in reaching thefloor(P<0.05).Staining of Nissl showed that the number of neurons in SNpc was significantly reduced(P<0.05).The expression of TH in SNpc and STR was significantly reduced(P<0.05);compared with group MPTP,the time of reaching in group MPTP+G-CSF was significantly shortened(P<0.05),neuron loss was reduced(P<0.05),and the morphology of neurons was relatively complete;compared with group MPTP,the MPTP+G-CSF group showed a significantly higher expression level of TH in SNpc and STR(P<0.05).Conclusion:G-CSF can improve the motor function of PD mice,reduce the loss of DA in the SNpc,and increase the expression level of TH.