溶酶体抑制剂对小鼠行为学与黑质多巴胺神经元的影响  

Damaging Effects of Lysosome Inhibitor on Dopaminergic Neurons in Substantia Nigra of Mouse Brain and Behavior of the Mice

作　　者：王法祥[1] 彭国光[1] 

机构地区：[1]重庆医科大学附属第一医院神经内科,重庆市神经病学重点实验室,重庆400016

出　　处：《中国实验动物学报》2009年第3期193-196,I0004,共5页Acta Laboratorium Animalis Scientia Sinica

摘　　要：目的初步探讨溶酶体抑制剂对小鼠行为学及多巴胺神经元功能的影响。方法于小鼠右侧中脑黑质(SN)区,立体定向微量注入溶酶体抑制剂和蛋白酶体抑制剂。观察阿朴吗啡诱导的小鼠旋转行为改变以及行为学变化;检测黑质区酪氨酸羟化酶(TH)阳性细胞数。结果阿朴吗啡未能诱导出小鼠旋转行为。蛋白酶体抑制剂组为10～15圈。多巴胺损害程度与溶酶体的剂量相关。磷酸氯喹25μmol/L时多巴胺神经元几乎没有损害作用;50μmol/L时局部区域多巴胺神经元有轻微损害;100μmol/L时损害明显;200μmol/L时黑质区注射局部神经元损害最严重,黑质注射区未见有神经元存在。1～4周呈现出较为明显逐渐恢复的特点。结论溶酶体功能抑制与多巴胺神经元凋亡相关,不同剂量溶酶体抑制剂在不同时间对多巴胺神经功能的损害不同。Objective To study the effects of lysosome inhibitor on the function of dopaminergic neurons in substantia nigra of mouse brain, and the behavior of ther mice. Methods Chloroquine phosphate in 5 μL （25,50,100,200μmol/L） and proteasome inhibitor MG-132 （10 μL/5 μL） were injected into the substantia nigra （SN） area in the mouse brain at the right side by stereotactic microinjection. The spontaneous and the apomorphine （ APO）-induced contralateral rotational behavior of mice was subsequently observed. The changes of tyrosine hydroxylase （TH） activity in the substantia nigra was assessed by immunohistochemistry. Results Almost no damage was revealed in the dopamine neurons in the 25 μmol/L chloroquine phosphate-treated mice, and slight damage in dopaminergic neurons in local area of the 50 μmol/L chlnroquine phosphate-treated mice. Distinct damages were observed in local dopaminergic neurons in SN treated with 100 μmol/L chloroquine phosphate. The dopaminergic neurons in local areas in the substantia uigra were severely damaged by 200 μmol/L chloroquine phosphate, so that very few dopaminergic neurons could be seen in the substantia nigra. Similar changes were observed in the G-132-treated mice. There have rotational behaviors 1 or 2 times occasionally in the mice of 100 μmol/L - 200 μmol/L lysosome inhibitor group and 10 - 15 r/min in the mice of proteasome inhibitor group by APO induced. Conclusion The results of this study demonstrate that there is a correlation between the lysosome dysfunction and damages of dopaminergic neurons, and show different damaging effects of different dose and time of lysosome inhibitor administration on the function of dopaminergic neurons.

关 键 词：帕金森病 溶酶体抑制剂 行为学 多巴胺神经元 

分 类 号：R754.2[医药卫生—皮肤病学与性病学]