神经生长因子鼻腔给药对MPTP致帕金森病模型小鼠的神经保护作用

Neuroprotective effect of intranasal administration of nerve growth factor in the mouse MPTP model of Parkinson's disease

目的:观察神经生长因子(nerve growth factors,NGF)鼻腔给药对于1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)所致的帕金森病模型小鼠的神经保护作用。方法:通过自主活动实验和滚筒实验研究动物的行为表现,通过高效液相电化学检测方法观察脑纹状体多巴胺的变化,检测纹状体内超氧化物歧化酶(SOD)以及谷胱甘肽-S转移酶(GSH-S)的活性。通过脑黑质酪氨酸羟化酶(tyroxine hydroxylase,TH)免疫组化染色观察多巴胺能神经元的损伤程度。结果:在注射MPTP前鼻腔给予NGF,能够改善其行为学,增加纹状体内多巴胺及其代谢产物的含量,增加纹状体内SOD以及GSH-S的活性,差异均有统计学意义(P<0.05或0.01)。免疫组织化学结果表明,鼻腔给予NGF后,TH阳性细胞数有所增加。结论:NGF鼻腔给药对于MPTP模型具有神经保护作用。

Objective ： To investigate the neuroprotective effect of intranasal administration of nerve growth factor （ NGF ） against 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine （ MPTP ）-induced dopaminergic toxicity. Methods： The behaviors of C57 mice were assessed using the spontaneous movement and rotarod tests. DA levels in the striatum were measured using HPLC-EC. We also determined the activities of SOD and GSH-S in the stria- turn. Dopaminergic neurons in the substantia nigra were observed by immunohistochemical staining with anti-tyrox- ine hydroxylase（TH） antibody. Results： When intranasally administered before MPTP, NGF reduced behavioral deficits, increased the levels of dopamine and dopamine metabolites in the striatum, and increased striatal SOD and GSH-S activity as compared to mice treated with MPTP alone. Immunohistochemical study with anti-tyrosine hydroxylase antibody showed that intranasal administration of NGF had a protective effect against MPTP-induced neuronal damage in the substantia nigra of mice. Conclusion： When intranasally administered before MPTP, NGF may be able to protect C57 mice against MPTP-induced neuronal damage.