摘要
目的 :观察左旋多巴 (L dopa)治疗对帕金森病 (PD )大鼠纹状体强啡肽原表达的影响 ,探讨L dopa诱发异动症 (LID)的机制。方法 :SD大鼠 36只 ,随机分为PD组、LID组和正常组。PD组及LID组大鼠以 6 OHDA损毁单侧黑质致密部建立PD模型 ,LID组 2周后腹腔注射L dopa甲酯 +苄丝肼 ,每日 2次 ,持续 4周 ,制备LID大鼠模型。分别取各组大鼠纹状体组织检测强啡肽原 (Prodynorphin ,PDyn)mRNA的表达水平。结果 :LID组大鼠L dopa治疗过程中 ,大多数出现继发异常不自主运动障碍 ,累及损毁对侧头、躯干、前肢和口面部肌肉。PD大鼠损毁侧纹状体内PDynmRNA水平较正常组大鼠减低 (P <0 .0 1) ,而反复L dopa治疗导致其表达水平明显高于其它 2组 (P <0 .0 1)。结论 :长期间断应用L dopa导致多巴胺缺失的纹状体区表达D1受体γ 氨基丁酸 (GABA)神经元选择性活化 。
Objective: To observe the effect of chronic levodopa (L dopa) administration on striatal prodynorphin mRNA expression in a rat model of Parkinson disease (PD), and probe into the pathogenesis of L dopa induced dyskinesias (LID). Methods: Thirty six Sprague Dawley rats were divided into three groups at random: PD group, LID group and normal group. A rat model of PD was made by unilateral lesion in the substantia nigra pars compact with 6 hydroxydopamine. Two weeks later, PD rats received daily injections of L dopa methyl ester plus benseraside in abdominal cavity, twice a day for 4 weeks. Levels of prodynorphin mRNA in the striatum were measured by in situ hybridization histochemistry. Results: In most of PD rats, chronic L dopa administration induced abnormal involuntary movements affecting cranial, trunk, forelimb and jaw muscles on the side of the body contralateral to the lesion. Levels of prodynorphin mRNA in the dopaminergic denevated caudate putamen of PD rats were lower than in the normal rats ( P <0.01), but as compared with other two groups, the expression of prodynorphin mRNA was significantly increased after repeated L dopa treatment ( P <0.01). Conclusion: Selective activation of GABA neuron expressing D1 receptors in the dopaminergic denevated caudate putamen after intermittent L dopa treatment and the secondary increase of striatal prodynorphin mRNA levels may be involved in the pathogenesis of LID.
出处
《中国康复》
2004年第3期142-144,共3页
Chinese Journal of Rehabilitation
基金
国家自然科学基金项目 (No :3 0 3 0 0 114 )
