多巴胺D2受体缺失加剧MPTP诱导的小鼠帕金森病样改变  

Lack of dopamine D2 receptor exacerbates MPTP-induced Parkinson's disease in mice

作　　者：黄彦[1] 曹蓓蓓[1] 刘展[1] 邱一华[1] 

机构地区：[1]南通大学医学院生理学系,南通226001

出　　处：《第二军医大学学报》2014年第12期1353-1357,共5页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(81271323);江苏省自然科学基金(BK2011386)~~

摘　　要：目的探讨多巴胺D2受体与帕金森病的运动行为学及发病间的关系。方法 C57BL/6野生型及D2受体基因敲除小鼠腹腔注射1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)制备帕金森病模型,爬杆实验、游泳实验观察比较两组小鼠行为学的改变,免疫荧光染色法观察小鼠中脑黑质致密部TH阳性神经元数目的变化。结果 MPTP注射后,小鼠爬杆实验时间延长,游泳实验评分降低,中脑黑质致密部TH阳性神经元数目下降(P<0.05或P<0.01);且D2受体基因敲除小鼠的行为学改变及TH神经元数目的减少较野生型小鼠更为明显(P<0.05或P<0.01)。结论多巴胺D2受体在小鼠肢体运动协调方面起着重要作用,D2受体缺失加剧了MPTP诱导的小鼠帕金森病样改变。Objective To investigate the association of dopamine D2 receptor with motor behavior and pathological characteristics of Parkinson＇s disease. Methods Wild type C57BL/6 mice （WT） and D2 receptor gene knockout mice （D2 -/- ） were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） to induce Parkinson＇ s disease （PD） models. Pole test and swim test were used to observe the motor behaviors of mice. Immunofluorescence staining was used to observe tyrosine hydroxylase （TH）-positive neuron numbers in the substantia nigra of the midbrain. Results After MPTP injection, the animals had a significantly longer time in pole testing, a significantly decreased score in swimming test, and a significantly decreased number of TH-positive neurons in the substantia nigra of the midbrain（P〈0. 05 or P〈0. 01）. Moreover, the behavioral changes and the decrease of TH-positive neuron numbers in D2-/- mice were more significant than those in the WT mice（P〈0.05 or P〈0. 01）. Conclusion Dopamine D2 receptor plays an important role in motor behavior of PD mice, and lack of dopamine D2 receptor exacerbates the symptoms of MPTP induced Parkinsoffs disease.

关 键 词：帕金森病 多巴胺D2受体 基因敲除小鼠 MPTP中毒 

分 类 号：R742.5[医药卫生—神经病学与精神病学]