XE991对6-OHDA诱导帕金森病模型大鼠运动行为影响

EFFECTS OF XE991 ON MOTOR BEHAVIOR IN 6-OHDA-INDUCED PARKINSON'S DISEASE RAT MODELS

目的探讨KCNQ通道抑制剂XE991对6-羟基多巴胺(6-OHDA)诱导的帕金森病(PD)模型大鼠行为学的影响。方法成年雄性Wistar大鼠48只,随机分为对照组、6-OHDA组和XE991+6-OHDA组。采用脑立体定位技术于大鼠中脑内侧前脑束给予6-OHDA制备PD大鼠模型。XE991+6-OHDA组在6-OHDA处理同时,每日侧脑室微量注射10μmol/L的XE991。对照组以等量生理盐水取代6-OHDA和XE991。在第7、14天检测3组大鼠由阿扑吗啡(APO)诱发的旋转行为的变化。结果术后第7、14天,6-OHDA组大鼠旋转圈数明显高于对照组,差异有显著意义(F=341.345、105.698,q=24.307、14.465,P<0.01);侧脑室注射XE991可以明显改善6-OHDA诱导的上述旋转行为,且差异有显著性(q=20.270、9.354,P<0.01)。结论 XE991可使6-OHDA诱导的PD模型大鼠运动能力有所改善。

Objective To investigate the effect of KCNQ channel inhibitor（XE991）on motor behavior of model rats in 6-OHDA-induced Parkinson＇s disease（PD）. Methods Forty-eight male adult Wistar rats were divided into three groups-control group,6-OHDA group and XE991＋6-OHDA group-in random.Using stereotaxic technology,the rats in 6-OHDA group were injected with 6-OHDA into the forebrain bundle of the midbrain to create a PD model.The rats in 6-OHDA＋XE991group were microinjection with XE991（10μmol/L,i.c.v.）,into lateral ventricle at the same time of 6-OHDA administration,and those in the control group were given equal amount of normal saline to replace 6-OHDA and XE991.The changes in rotational behavior induced by apomorphine（APO）were detected in rats of the three groups-on days 7and 14 of the experiment. Results On days7 and 14 after the experiment,the number of turns in rats of 6-OHDA group was obviously higher than that of the control group（F=341.345,105.698;q=24.307,14.465;P〈0.01）.Lateral ventricle injection of XE991 can significantly improve the above rotation behavior induced by 6-OHDA,the difference being significant（q=20.270,9.354;P〈0.01）. Conclusion XE991 may improve motor ability of 6-OHDA-induced Parkinson＇s disease model rats.