半胱氨酰白三烯受体CysLT_1R和CysLT_2R以及GPR17在帕金森病模型小鼠脑内的表达分布  

Expression and distribution of cysteinyl leukotriene receptors CysLT_1R and CysLT_2R,and GPR17 in brain of Parkinson disease model mice

作　　者：王浩[1,2] 石巧娟[2] 史文珍[2] 张霞燕[2] 王晓蓉[2] 张丽慧[3] 方三华[2] 卢韵碧[2] 张纬萍[2] 魏尔清[2] 

机构地区：[1]浙江省立同德医院神经内科,浙江杭州310012 [2]浙江大学医学院药理学系,浙江杭州310058 [3]杭州师范大学基础医学部药理学教研室,浙江杭州310036

出　　处：《浙江大学学报（医学版）》2013年第1期52-60,共9页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金项目(81072618);浙江省自然科学基金项目(LY12H31010);杭州师范大学国家项目培育基金(2010PYjj41)

摘　　要：目的:探讨MPTP小鼠帕金森病(PD)模型脑内半胱氨酰白三烯受体CysLT1R、CysLT2R和GPR17表达分布特征。方法:C57BL/6小鼠连续5 d皮下注射MPTP 25 mg/kg诱导PD模型,第10 d处死动物。应用免疫组化方法,观察CysLT1R、CysLT2R和GPR17在黑质表达的变化,并用免疫双标方法进行细胞定位。结果:正常小鼠黑质中有CysLT1R、CysLT2R和GPR17表达,主要表达在TH阳性多巴胺能神经元以及小胶质细胞,CysLT2R还表达于星形胶质细胞;其中,在多巴胺能神经元中91%表达GPR17,77%表达CysLT1R,52%表达CysLT2R。与对照组比较,PD模型组小鼠黑质中TH阳性细胞数显著减少;同时CysLT1R、CysLT2R和GPR17阳性细胞数以及表达CysLT1R、CysLT2R和GPR17的多巴胺细胞数均显著减少。在正常小鼠纹状体中有CysLT1R、GPR17表达,主要表达于神经元;而CysLT2R表达很少,主要表达于星形胶质细胞。PD模型组小鼠纹状体中CysLT1R、GPR17阳性细胞数减少;但CysLT2R表达升高,主要表达于增生的星形胶质细胞。结论:CysLT1R、CysLT2R和GPR17可能参与MPTP所致的小鼠PD损伤过程。Objective ： To examine the spatiotemporal profiles and localization of CysLTj R, CysLT2 R and GPR17 in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP）-indueed Parkinson disease （PD）. Methods： PD model was induced by subcutaneous injection of MPTP （25 mg/kg） for 5 d in adult male C57BL/6 mice. At d10 after MPTP injection, the expression and cellular localization of CysLTIR, CysLT2 R and GPR17 in the substantia nigra were detected by immunohistochemistry and immunofluorescence. Results： CysLT1 R, CysLT2R and GPR17 were normally localized in TH-positive dopaminergic neurons and microglia, while CysLT2 R was also expressed in astrocytes. In dopaminergic neurons,approximately 91% co-expressed GPR17,77% co-expressed CysLT1R and 52% co-expressed CysLT2R. Compared with the control group, TH-positive cells in the substantia nigra were significantly reduced in PD mice. CysLTt R, CysLT2 R and GPR17-positive cells were significantly reduced; and CysLT1 R, CysLT2 R, GPR17-positive dopaminergic neurons were also significantly reduced in the PD group. In the striatum,both CysLT1R and GPR17 were normally expressed in neurons; whereas CysLT2R was expressed in astrocytes. In PD striatum, CysLT1 R and GPR17-positive cells were decreased, but CysLTiR expression was significantly increased which mainly expressed in the proliferating astrocytes. Conclusion： CysLT1 R,CysLT2Rand GPR17 may be involved in the MPTP-induced PD damage in mice.

关 键 词：半胱氨酸 受体 白三烯 受体 G-蛋白偶联 帕金森病 疾病模型 动物 免疫组织化学 

分 类 号：R742.5[医药卫生—神经病学与精神病学]