左旋多巴诱发异动症大鼠纹状体缝隙连接蛋白CX36表达增强

目的:观察左旋多巴诱发异动症(LID)大鼠模型缝隙连接蛋白36(CX36)表达,初步探讨缝隙连接在LID形成机制中的作用。方法:制备帕金森病(PD)和LID大鼠模型,将实验动物分3组:LID模型组、PD未治疗组、正常对照组。各组大鼠分2亚组(缝隙连接阻断剂处理组和生理盐水对照组),观察系统途径给予缝隙连接阻断剂甘珀酸(carbenoxolone)对各组大鼠不自主运动行为的影响。利用免疫组化法检测各组大鼠脑皮层运动区和纹状体区CX36表达并进行分析比较。结果:腹腔注射缝隙连接阻断剂甘珀酸对阿扑吗啡诱导的LID不自主运动和PD旋转行为均无明显影响(P>0.05)。免疫组化结果显示LID组皮层运动区和纹状体区CX36表达较PD组和正常组均有显著增多(P<0.05),PD组与正常对照组亦有明显差别(P<0.05)。结论:LID大鼠基底节及大脑皮层CX36表达增加,缝隙连接可能参与了LID的形成机制。

Increased expression of gap junction protein connexin 36 in the striatum of rat with levodopa-induced dyskinesia

Objective: To observe the expression of connexin 36(CX36) in the brain of levodopa-induced dyskinesia(LID) rat model,and explore the role of gap junction in the pathogenesis of LID.Methods: Hemi-parkinsonism(PD) and LID rat models were made.The experimental animals were divided into three groups: LID group,PD group and normal control group,respectively.Each group was divided into two subgroups(carbenoxolone and saline groups).Then,the apomorphine induced abnormal involuntary movement(AIM) and rotational behavior in responese to gap junction blocker carbenoxolone given by intraperitoneal injection were assessed.After the behavior testing,the rats were executed and processed for examining CX36 expression in the striatum and cortex by immunohistochemistry.Results: Carbenoxolone injected intraperitoneally showed no significant effects on apomorphine-induced AIM in LID rats and on apomorphine-induced rotational behavior in PD rats(P>0.05).The expression of CX36 in striatum and motor cortex of LID rats was significantly increased compared with PD model or the normal control rats(P<0.05).Compared with the normal control group,CX36 expression in these brain regions in the PD model group was also elevated(P<0.05).Conclusion: The expression of connexin 36 in the striatum and cerebral motor cortex were increased in LID rats,gap junction dysfunction may play a role in the pathogenesis of LID.