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  

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

作　　者：胡丹[1] 曹卫[2] 孙圣刚[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,武汉430022 [2]华中科技大学同济医学院附属协和医院核医学科,武汉430022

出　　处：《神经损伤与功能重建》2007年第6期329-332,共4页Neural Injury and Functional Reconstruction

基　　金：国家自然科学青年基金项目(30400516);武汉青年科技晨光计划(20045006071-2)

摘　　要：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。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 E2 mg/（kg/d）, 5 times/day× 17d, i. p. ];4 mice （Nic-＋MPTP group） pretreated with nicotine for 10 days before MPTP injection; and 4 mice （control group） injected with equivalent volume of normal saline. The number and apoptosis of dopaminergic 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.

关 键 词：帕金森病 1-甲基-4-苯基-1 2 3 6-四氢吡啶 尼古丁 

分 类 号：R741[医药卫生—神经病学与精神病学] R742.5[医药卫生—临床医学]