MPTP诱导多巴胺能神经元凋亡规律和尼古丁神经保护作用的研究

目的:探讨1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导小鼠多巴胺能神经元凋亡的规律以及尼古丁对其的保护作用。方法:取28只小鼠(PD组)腹腔注射MPTP 30 mg/(kg·d),共7 d,建立小鼠帕金森病模型;取4只小鼠(Nic组)腹腔注射尼古丁(2 mg/kg,每天5次,共17 d);取4只小鼠(Nic+MPTP组)给予尼古丁预处理和MPTP;取4只小鼠(对照组)仅给予等量生理盐水。应用酪氨酸羟化酶(TH)免疫组织化学染色和TUNEL染色,观察各组黑质多巴胺能神经元数目改变和凋亡细胞的变化规律。结果:慢性MPTP处理过程中,小鼠黑质TH阳性细胞数逐渐减少,于MPTP注射第3天开始出现TUNEL阳性细胞,并于第8天达到高峰。与PD组相比,Nic+MPTP组TH阳性细胞丢失和TUNEL阳性细胞增多的程度显著降低(P<0.05)。结论:采用慢性MPTP处理的模式,可诱导小鼠黑质多巴胺能神经元凋亡;尼古丁对这类神经元具有明显保护作用。

A Study of Apoptosis in Dopaminergic Neurons Induced by MPTP and Protective Effects of Nicotine

Objective:To investigate apoptosis of dopaminergic neurons and protective effects of nicotine in MPTP-induced Parkinson's disease (PD) mouse model.Methods:28 mice (PD group) were injected with MPTP 30 mg/(kg/d)]intraperitoneally for 7 days to establish a mouse model of Parkinson's disease;4 mice (Nic group) treated with nicotine 2 mg/(kg/d),5 times/day×17d,i.p.];4 mice (Nic+MPTP group) pretreated with nico- tine for 10 days before MPTP injection;and 4 mice (control group) injected with equivalent volume of normal sa- line.The number and apoptosis of dopammergic neurons were detected by TH and TUNEL staining.Results:The number of TH-positive cells decreased gradually after MPTP administration.TUNEL-positive cells began to appear on day 3 and peaked on day 8 after MPTP injection.In the Nic+MPTP group,the loss of TH-positive cells and number of TUNEL-positive cells in the substantia nigra decreased significantly when compared to the PD group (P<0.05).Conclusion:Chronic administration of MPTP to mice could induce apoptosis of dopaminergic neurons in substantia nigra,and nicotine might alleviate its neurotoxicity.