缝隙连接蛋白Cx36在左旋多巴诱发异动症大鼠发病机制中的作用

Research on Role of Connexin 36 in Pathogenesis of Rats with Levodopa-induced Dyskinesia

目的:研究纹状体区缝隙连接蛋白36(Cx36)在左旋多巴诱发的异动症(LID)形成机制中的作用。方法:60只SD大鼠按照随机数字表分成正常组、假手术组、帕金森病(PD)组、观察组和雷帕霉素对照组,每组12只。向右侧内侧前脑束注射6-羟多巴(6-OHDA)建立偏侧PD大鼠模型,以左旋多巴治疗PD大鼠,制作LID大鼠模型,观察组造模后给予左旋多巴连续治疗3周,雷帕霉素对照组造模后在左旋多巴治疗的同时,给与雷帕霉素干预。正常组、假手术组、PD组不做任何治疗或只给与安慰剂。采用不自主运动(AIM)评分评估观察组和雷帕霉素对照组大鼠不自主运动的行为学改变,运用免疫组化技术检测5组大鼠纹状体区右侧Cx36表达,探讨Cx36表达水平与行为学的关系。结果:观察组大鼠的AIM评分明显高于雷帕霉素对照组,差异有统计学意义(P<0.05);观察组损毁侧纹状体区Cx36表达明显高于其余4组(P<0.01);Cx36表达和AIM评分成正相关。结论:Cx36的表达水平的增高与LID的形成关系密切。Cx36的表达上调可能强化了纹状体神经元同步化振荡放电,加剧纹状体区多巴胺能神经元内直接通路和间接通路的失衡,促成纹状体异常信号的输出,最终导致LID的形成。

Objective： To study the role of striatal connexin 36 （Cx36） in the pathogenesis of levodopa-induced dyskinesia （LID）. Methods ：A total of 60 SD rats were divided into the normal group, the sham operation group, the Parkinson＇s disease （PD） group, the experimental group and the control group by a random number table ,and 12 rats in each group. The hemi-PD rat models were es- tablished by 6-Oxidopamine （6-OHDA） microinjection into right medial forebrain bundle （MFB）, then PD rats received intraperi- toneal injection of levodopa for a week to establish a LID rat model. The experiment group and the control group were given levodopa for another two weeks, and the control group was added with rapamycin at the same time. The normal group, the sham operation group and the PD group received no treatment or only placebo. The behavioral changes in the experimental group and the control group were observed by abnormal involuntary movement （AIM） score, the Cx36 expression in the right striatum in the five groups were detect- ed by immunohistochemisty, and the relationship between Cx36 expression and behavior was investigated. Results：The AIM scores in the experimental group was higher than that of the control group （P〈 0.05 ） ;the expression of Cx36 in the injured side of s triatum in the experimental group was higher than that of the other four groups （P〈 0.01 ） ;and the Cx36 expression was positively related to AIM scores. Conclusion：The increase of Cx36 expression is closely related to the pathogenesis of LID. The up-regulation of Cx36 ex- pression may increase the oscillatory discharge of neurones, and enhance the unbalance of the direct and indirect pathways in the stria- turn, and promote the output of abnormal striatal signals, which leads to the formation of LID.