亲代谢型谷氨酸受体配基对帕金森病大鼠的神经保护作用  

Neuroprotection of metabotropic glutamate receptors ligand in Parkinson disease model rat

作　　者：顾兵[1] 张颖冬[2] 胡刚[1] 

机构地区：[1]南京医科大学药理学与神经生物学系,江苏省南京市210029 [2]南京医科大学附属脑科医院神经内科,江苏省南京市210029

出　　处：《中国临床康复》2003年第16期2261-2263,T001,共4页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金资助项目(39970846);2000年教育部优秀青年教师资助计划项目(1656)~~

摘　　要：目的探讨PD模型大鼠黑质致密部亲代谢型谷氨酸受体(mGluRs)的蛋白表达及其配基的药物治疗作用。方法6-羟基多巴单侧黑质损毁法建立大鼠PD模型。免疫组织化学法观察黑质致密部mGluR1a,2/3,4,5,8和酪氨酸羟化酶(TH)的表达,并用Nissl和Fluoro-JadeB荧光双染法在激光共集焦显微镜下观察退行性变的神经元。结果6-羟基多巴导致损毁侧mGluRs和TH免疫活性下降。Ⅰ组mGluRs拮抗剂和Ⅱ,Ⅲ组mGluRs激动剂能使治疗组相应的受体表达升高,尤其是mGluR5,mGluR2/3和mGluR4的蛋白表达。其中,以APDC组(Ⅱ组mGluRs激动剂)的保护效应最为显著。5个非假手术组退行性变细胞与正常细胞的比值(D/V)均有不同程度地增高。结论mGluRs可能参与PD的发生、发展过程。Ⅰ组mGluRs拮抗剂和Ⅱ组mGluRs激动剂具有一定的神经保护功能。Aim To explore the expression of metabotropic glutamate receptors(mGluRs)protein in rats bearing a complete unilateral substantia nigra pars compacta (SNc) lesion and the pharmacological effect of mGluRs ligands.Methods The PD rat models were established by employing 6 hydroxydopamine to lesion unilateral substantia nigral.The immunohistochemical method was used to examine the effect of 6 hydroxydopamine lesions of SNc on the expression of mGluRs (mGluR1a, 2/3, 5, 4, 8) protein and tyrosine hydroxylase (TH).Meanwhile,the degenerative neurons were observed under laser confocal microscopy by means of double staining that combined Fluoro Jade B with fluorescent Nissl counterstain. Results 6 Hydroxydopamine caused a decrease in the number of mGluRs and TH in the lesioned lateral substantia nigra.Pharmacological activation of groupⅡor ⅢmGluRs or blockade of groupⅠmGluRs for one week was normalized to a distinct degree on the expression of the iso group receptors, especially that of mGluR5, 2/3, 4 protein. Among them,the effect of APDC (groupⅡmGluRs selective agonist) was insignificant.The ratios of degenerating cells to viable cells (D/V) in five non Sham groups all increased at different levels.Conclusion mGluRs may be involved in the progression of PD.The alteration in the receptor expression may be a compensatory mechanism developed after neuroprotective treatment by antagonist of groupⅠand agonist of groupⅡmGluRs.

关 键 词：亲代谢型谷氨酸受体 配基 帕金森病 大鼠 神经保护作用 药物治疗 蛋白表达 

分 类 号：R742.5[医药卫生—神经病学与精神病学]