4-AP对MPTP诱导PD模型小鼠运动行为影响

EFFECT OF 4-AP ON MOTOR BEHAVIOR IN MPTP MOUSE MODEL OF PARKINSON'S DISEASE

目的探讨A型钾通道抑制剂4-氨基吡啶(4-AP)对l-甲基4苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠运动行为的影响。方法 8周龄雄性C57BL/6小鼠30只,随机分为对照组、MPTP组以及4-AP+MPTP组,每组10只。采用连续5d腹腔注射MPTP(30mg·kg-1·d-1)的方法制备PD小鼠模型。4-AP+MPTP组在每天注射MPTP前30min腹腔注射4-AP(1mg·kg-1·d-1),对照组以等量生理盐水代替MPTP和4-AP。连续5d注射后进行爬杆实验检测。结果 MPTP组小鼠爬杆实验的转头时间和爬杆时间明显长于对照组,而4-AP+MPTP组小鼠转头时间和爬杆时间较MPTP组明显缩短,差异均有显著意义(F=32.26、25.53,P<0.01)。结论 4-AP可使MPTP诱导的PD模型小鼠运动协调能力有所改善。

Objective To investigate the effect of 4-aminopyridine(4-AP),an inhibitor of A-type potassium channel,on motor behavior in mice with Parkinson’s disease(PD)induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Methods Thirty 8-week-old male C57BL/6mice were randomly divided into MPTP group,4-AP+MPTP group,and control group,with 10mice per group.The mice in the MPTP group and 4-AP+MPTP group received intraperitoneal injection of MPTP(30mg·kg-1·d-1)for 5consecutive days to establish a mouse model of PD;in addition,the mice in the 4-AP+MPTP group were intraperitoneally injected with 4-AP(1mg·kg-1·d-1)30min before the daily injection of MPTP.As for the control group,MPTP and 4-AP were replaced by an equal volume of normal saline.The pole test was performed after 5consecutive days of injection.Results The time to turn around and time to reach the floor in the MPTP group were significantly longer than those in the control group,while they were significantly shortened in the 4-AP+MPTP group compared with the MPTP group(F=32.26and 25.53,P<0.01).Conclusion Inhibition of A-type potassium channel by 4-AP may attenuate motor coordination dysfunction in mice with MPTP-induced PD.