左旋多巴诱发异动症大鼠基底节环路功能改变的研究  

Abnormal activity of the basal ganglia circuit in the pathogenesis of levodopa-induced dyskinesias of rats

作　　者：牛轶瑄[1] 孙圣刚[1] 魏桂荣[1] 张允建[1] 徐岩[1] 曹学兵[1] 

机构地区：[1]武汉市华中科技大学同济医学院附属协和医院神经内科,430022

出　　处：《中华老年医学杂志》2007年第9期697-701,共5页Chinese Journal of Geriatrics

基　　金：国家自然科学基金资助项目（No：30300114）

摘　　要：目的研究左旋多巴诱发的异动症（LID）大鼠纹状体区前强啡肽原（PDyn）和神经生长因子诱导蛋白-B（NGFI-B）基因表达的变化与行为学特点,探讨LID时大鼠基底节环路功能改变与异动症形成之间的关系。方法分别以SCH23390（D1受体拮抗剂）、氟哌啶醇（D2受体拮抗剂）治疗LID大鼠,观察LID大鼠的行为学改变,并用逆转录聚合酶链反应技术检测其纹状体区PDyn mRNA和NGFI-B mRNA表达的变化。结果LID大鼠治疗第28天的异常不自主运动（AIM）评分为（43.3±11.3）分,经SCH23390治疗后为（4.5±2.2）（P〈0.01）,而经氟哌啶醇治疗后为（39.8±8.4）分,（P〉0.05）。大鼠损毁侧纹状体区PDyn mRNA的相对表达量：PD组为（0.95±0.31）低于LID组（1.80±0.28）（P〈0.01）,SCH23390组（1.13±0.39）低于LID组（P〈0.01）,氟哌啶醇组（1.69±0.92）则高于SCH23390组（P〈0.01）,上述差异均有统计学意义。NGFI-B mRNA的相对表达量：LID组（14.98±0.43）较PD组（11.38±1.02）增高（P〈0.01）,SCH23390组（14.26±0.69）与LID组比较,差异无统计学意义（P〉0.05）。氟哌啶醇组为（18.01±0.73）,分别高于LID组和SCH23390组（P均〈0.01）。结论LID的形成与基底节环路活动异常有关,其中直接通路的异常活化起了关键性的作用,直接通路上PDyn mRNA和NGFI-B mRNA表达的增高与LID的形成密切相关。Objective To study behavioral character and the expression change of nerve growth factor inducible protein B gene（NGFI-B）and prodynorphin（PDyn）in striatum,the functional alteration of the basal ganglia circuit in the pathogenesis of levodopa-induced dyskinesias（LID）. Methods The rat model of LID was treated with SCH 23390（a dopamine D1 antagonist）and haloperidol（a dopamine D2 antagonist）respectively.Reverse transcription-polymerase chain reaction （RT-PCR）was used to detect the expressions of NGFI-B mRNA and PDyn mRNA in striatum,and the behavior changes were observed.Results On the day 28,the abnormal involuntary movement （AIM）score of LID group（43.3±11.3）was significantly higher than that of 8CH23390 group（4.5±2.2）（P〈0.01）,and there was no significant difference in the score between Haloperidol group（39.8±8.4）and SCH23390 group（P〉0.05）.NGFI-B mRNA level in the denervated striatum was significantly higher in Haloperidol group（18.01±0.73）compared to LID group（14.98±0.43）（P〈0.01）,but there was no difference between that of SCH23390 group（14.26±0.69）and LID group（P〉0.05）.PDyn mRNA level was significantly higher in LID group（1.80±0.28）compared to SCH23390 group（1.13±0.39）（P〈0.01）or PD group（0.95±0.31）（all P〈0.01）respectively,but there was no difference between that of Haloperidol group（1.69±0.92）and LID group（P〉0.05）. Conclusions High levels of NGFI-B and PDyn in striatum,together with a persistent hyperresponsiveness of striatonigral neurons and hyporesponsiveness of striatopallidal neurons,by creating an unbalanced state of striatal efferent neurons,may be implicated in dyskinetic movements observed in Parkinson disease.

关 键 词：帕金森病 神经生长因子类 强啡肽类 

分 类 号：R686[医药卫生—骨科学]