代谢型谷氨酸受体5拮抗剂对临床早期帕金森病模型大鼠行为变化的影响及神经保护作用  

Effects of Chronic,Systemic Treatment with Metabotropic Glutamate Receptor 5 Antagonist on Behavioral Activity and Neuroprotection in a Preclinical Rat Model of Parkinson’s Disease

作　　者：陈丽[1] 刘健[1,2] 桂振华[1] 王勇[1] 向莉[3] 

机构地区：[1]西安交通大学医学院生理学与病理生理学系,西安710061 [2]教育部环境与疾病相关基因重点实验室,西安710061 [3]西安交通大学医学院第二附属医院神经内科,西安710004

出　　处：《四川大学学报（医学版）》2011年第1期65-68,共4页Journal of Sichuan University(Medical Sciences)

基　　金：陕西省自然科学基金(2007C205)资助

摘　　要：目的探讨代谢型谷氨酸受体5(mGluR5)拮抗剂6-甲基-2-苯基吡啶(MPEP)对黑质-纹状体通路部分损伤的帕金森病(PD)大鼠行为活动的影响及神经保护作用。方法雄性SD大鼠37只随机分为假手术组(11只)、生理盐水组(15只)和MPEP治疗组(11只)。生理盐水组和MPEP组内侧前脑束(MFB)注射6-羟多巴胺(6-OHDA)建立临床早期PD大鼠模型。术后第8d及15d分别对各组大鼠进行行为学和免疫组织化学检测,观察自发和诱发行为的变化及黑质致密部(SNpc)多巴胺能神经元丢失的比例。结果各组动物并未出现姿势异常。与假手术组相比,生理盐水组大鼠在术后第8d和第15d产生了明显的阿朴吗啡(APO)诱发旋转行为(P<0.05),且第15d较第8d严重(P<0.05),而APO未能诱发MEEP组大鼠的旋转行为(P>0.05)。免疫组化染色结果显示,生理盐水组SNpc约39%的多巴胺能神经元丢失,而MPEP治疗减轻了神经元的丢失(P<0.01)。结论在黑质-纹状体通路部分损伤的大鼠,MPEP治疗具有抗PD和神经保护效应。Objective To study the effects of chronic,systemic treatment with 2-methyl-6-（phenylethynyl）-pyridine（MPEP） on behavioral activity and neuroprotecion in the rat with partial lesion of the nigrostriatal pathway.Methods A total of 37 male SD rats were randomLy divided into sham（n=11）,PD＋saline（n=15） and PD＋MPEP group（n=11）.Rat model of Parkinson’s disease was established by injection of 6-OHDA into medial forebrain bundle.PD＋vehicle rats and PD＋MPEP rats were injected with NS（0.1 mL） and MPEP（3 mg/kg） per day respectively.Changes in the spontaneous and induced behaviors and the degree of dopamimnergic neurons loss in the substantia nigra pars compacta（SNpc） were observed by behavioral and immunocytochemical methods in partially lesioned and MPEP-treated rats.Results Unilateral injection of 6-hydrodopamine（6-OHDA） into medial forebrain bundle resulted in the moderate loss（39 %） of dopaminergic neurons in the SNpc,and MPEP treatment decreased the number of neurons loss compared with PD＋saline rats（P〈0.01）.In this model,the lesioned rats did not show obviously abnormal posture.However,apomorphine（APO） induced significant rotation behavior,which increases in a time-dependent manner.Chronic,systemic treatment with MPEP could against the toxicity of 6-OHDA,and reduced the loss of SNpc dopaminergic neurons.In addition,MPEP ameliorated significantly the rotation behaviour induced by APO,which is strengthened in a time-dependent manner.Conclusion MPEP treatment has anti-parkinsonian and neuroprotective effects in the rat with partial lesion of the nigrostriatal pathway,and the efficacy gradually increase with the treatment time.

关 键 词：帕金森病 神经保护作用 黑质致密部 6-甲基-2-苯基吡啶 

分 类 号：R742.5[医药卫生—神经病学与精神病学]