运动通过调节内源性大麻素系统抑制帕金森病模型大鼠纹状体谷氨酸兴奋性毒作用的实验研究  

Experimental Study that Treadmill Exercise Inhibit Striatal Glutamate Excitotoxicity by Regulating Endocannabinoid System in a Rat Model of Unilateral Parkinsonism

作　　者：林湘明[1] 刘晓莉[1] 时凯旋 张凌韬 张文津 

机构地区：[1]北京师范大学体育与运动学院,北京100875 [2]北京市第三十五中学国际部,北京100082

出　　处：《天津体育学院学报》2017年第3期261-268,共8页Journal of Tianjin University of Sport

基　　金：国家自然科学基金项目(项目编号:31571221)

摘　　要：目的:试图从内源性大麻素系统(e CBs)对纹状体突触Glu兴奋性毒性的调节作用入手,进一步阐释运动调控PD模型大鼠行为功能紊乱的神经生物学机制。方法:选用清洁级雄性SD大鼠,随机分为假手术组、假手术运动组、PD组、PD运动组,每组18只,共72只。6-OHDA于右内侧前脑束注射制备单侧PD大鼠模型,假手术组于相同位点注射等量生理盐水作为对照。术后恢复1周对大鼠进行强度11 m/min,时间30 min/d,每周5天,为期4周运动干预。在建模后7天于颈部皮下注射阿扑吗啡(APO)诱导旋转实验评价PD模型可靠性,并结合平衡木试验评价大鼠运动整合能力和平衡能力。采用微透析-高效液相色谱(HPLC)技术,检测纹状体神经细胞外Glu浓度;采用免疫组化和免疫印记技术检测纹状体CB1受体及RGS4蛋白表达。结果:运动干预第3、4周,与PD组相比,PD运动组大鼠穿越平衡木的潜伏期和总时间显著性减少(P<0.05),纹状体神经细胞外Glu含量显著降低(P<0.05),纹状体CB1受体、RGS4蛋白表达水平也显著降低(P<0.05)。结论:运动通过调节纹状体RGS4、CB1表达,降低纹状体胞外Glu增高的趋势,并改善了PD模型大鼠运动整合能力和平衡能力。e CBs参与运动对皮层-纹状体Glu突触兴奋性毒作用的调节过程,其机制可能与运动重塑皮层-纹状体Glu能突触e CBs介导的长时程抑制(e CB-LTD)有关。Objective：To further explain the biological mechanism of behavioral deficits in rats with PD model,we investigated the effects of endocannabinoidsystem（e CBs）on regulation of striatal Glu excitotoxicity. Methods：Seventy-two adult male SD rats were randomly divided into 4 groups：Control（Control）,Control with exercise（Control＋Ex）,PD（PD）,PD with exercise（PD＋Ex）,with 18 rats in each group. 6-OHDA was injected into the right medial forebrainbundle of rats to establish a unilateral PD rat model. The sham group was injected with the same amount of normal saline as the control group. One week aftersurgery,exercise group rats participated in 4 weeks exercise,exercise program was 11 m/min,30 min/day,and 5 days/week. At 7 days after surgery,subcutane-ous injection of Apomorphine induced rotation test performed to evaluate the reliability of PD model,and the balance beam test was used to examine the abili-ty of motor integration and balance. The extracellular Glu concentration was measured by microdialysis and high performance liquid chromatography（HPLC）.The expression of CB1 receptor and RGS4 protein was observed by immunohistochemical staining and western blotting. Results：After 3 and 4 weeks of exer-cise intervention,compared with PD group,PD exercise group rats through the balance beam latency and total time were significantly lower（P〈0.05）,the con-centration of Glu in striatum was significantly decreased（P 0.05）. the expression of striatal CB1 receptor and RGS4 protein levels were significantly decreased（P〈0.05,P〈0.05）. Conclusions：Exercise regulates the expression of RGS4 and CB1,reduced the trend of increased extracellular Glu in striatum,and im-proved the motor integration ability and balance ability of PD rats. e CBs participates the regulation of excitotoxicity in corticostriatal Glu synapses. It is specu-lated that the mechanism of exercise remodel corticostriatal synaptic plasticity was related to recovery of the endocannabinoid-dependent LTD（e CB-LTD）.

关 键 词：帕金森病 大鼠 运动干预 谷氨酸 内源性大麻素系统 

分 类 号：G804.2[文化科学—运动人体科学]