运动通过上调mGluR2/3表达抑制帕金森病模型大鼠纹状体中等多棘神经元异常电活动  

Exercise Inhibits the Abnormal Electrical Activity of Striatal Medium Spiny Neurons in Parkinson’s Disease Model Rats by Up-regulating mGluR2/3 Expression

作　　者：陈平[1,2] 耿小飞 刘晓莉 乔德才[1] Chen Ping;Geng Xiaofei;Liu Xiaoli;Qiao Decai(College of Physical Education and Sports,Beijing Normal University,Beijing 100875,China;College of Physical Education,Jishou University,Jishou 416000,China;College of Physical Education,Hebei Ethnic Normal University,Chengde 067000,China)

机构地区：[1]北京师范大学体育与运动学院,北京100875 [2]吉首大学体育科学学院,湖南吉首416000 [3]河北民族师范学院体育学院,河北承德067000

出　　处：《中国运动医学杂志》2022年第7期523-534,共12页Chinese Journal of Sports Medicine

基　　金：国家自然科学基金(31571221)。

摘　　要：目的:探讨运动通过上调代谢型谷氨酸受体2/3(mGluR2/3)表达对帕金森病(PD)模型大鼠纹状体中等多棘神经元(MSNs)异常电活动的影响。方法:清洁级SD大鼠随机分为假手术安静组(Control组,n=9)和6-羟基多巴胺(6-OHDA)造模组(6-OHDA组,n=40)。6-OHDA造模组采用神经毒素6-OHDA注射于大鼠右脑内侧前脑束(MFB),建立偏侧损毁PD模型大鼠,假手术组于相同部位给予同等剂量的生理盐水作为对照组。采用阿扑吗啡(APO)诱导旋转行为测试评价PD模型的可靠性。经鉴定符合PD模型的大鼠随机分为6-OHDA安静组(PD组,n=9)、6-OHDA+运动组(PD+Ex组,n=9)和6-OHDA+运动+mGluR2/3拮抗剂组(PD+Ex+APICA组,n=9)。运动组于手术后1周开始进行跑台训练干预(11 m/min,30 min/day,5 d/week,4 weeks)。运动+mGluR2/3拮抗剂组每次运动前,采用微量注射泵将mGluR2/3拮抗剂APICA注射到纹状体内,注射体积为1μL。采用免疫组织化学染色技术检测黑质酪氨酸羟化酶(TH)免疫阳性细胞数量和纹状体TH免疫阳性纤维终末含量。采用免疫印迹技术检测纹状体mGluR2/3的表达水平。采用多通道电生理记录系统对各组大鼠清醒静止状态下纹状体神经元电活动进行记录。结果:APO诱导的旋转行为测试和TH免疫组织化学检测结果表明,PD大鼠模型可靠,成模率为67.5%。免疫印迹技术检测结果显示,与Control组相比,PD组纹状体mGluR2/3表达水平显著下调(P<0.01);与PD组相比,PD+Ex组纹状体mGluR2/3表达水平显著上调(P<0.05)。电生理分析结果表明,与Control组相比,PD、PD+Ex和PD+Ex+APICA组纹状体MSNs平均放电频率均显著增加(P<0.01);与PD组相比,PD+Ex组纹状体MSNs平均放电频率显著降低(P<0.05);与PD+Ex组相比,PD+Ex+APICA组纹状体MSNs平均放电频率显著增加(P<0.01)。与Control组相比,PD组纹状体神经元局部场电位(LFPs)在β频段(10~30 Hz)节律性振荡功率出现异常增加(P<0.01),PD+Ex组纹状体神经元LFPs在β频段(1Objective To explore the effect of exercise on the inhibition of abnormal electrical activi⁃ty of medium spiny neurons(MSNs)in the striatum of Parkinson’s disease(PD)model rats by up-regu⁃lating the expression of metabotropic glutamate receptor 2/3(mGluR2/3).Methods Clean Sprague-Daw⁃ley rats were randomly divided into a sham operation quiet group(Control,n=9)and a 6-hydroxydopa⁃mine(6-OHDA)model group(6-OHDA,n=40).In the 6-OHDA model group,neurotoxin 6-OHDA was injected into the medial forebrain bundle(MFB)of the right brain to establish PD model rats with hemiplegic lesions,and the sham group was given the same dose of saline at the same site as the control group.Apomorphine(APO)induced rotational behavior test was used to evaluate the reliability of the PD model.Then rats successfully modeled were randomly assigned to a 6-OHDA quiet(PD,n=9),a 6-OHDA+exercise(PD+Ex,n=9)and a 6-OHDA+exercise+mGluR2/3 antagonist group(PD+Ex+APICA,n=9).One week after surgery,treadmill training intervention(11 m/min,30 min/day,5 days/week for 4 weeks)was initiated in the exercise group.Before each exercise session in the exercise+mGluR2/3 antagonist group,1-μL mGluR2/3 antagonist APICA was injected into the stria⁃tum using a microinjection pump.Immunohistochemical staining was used to detect the number of tyro⁃sine hydroxylase(TH)immunopositive cells in the substantia nigra and the terminal content of TH im⁃munopositive fibers in the striatum.Western blotting was employed to detect the expression level of mGluR2/3 in the striatum.A multichannel electrophysiological recording system was used to record the electrical activity of striatal neurons in each group of rats in conscious and quiescent conditions.Re⁃sults The results of APO-induced rotational behavior test and TH immunohisto-chemistry showed that the PD rat model was reliable,with a successful modeling rate of 67.5%.Western blotting showed that striatal mGluR2/3 expression levels down-regulated significantly in the PD group compared with the control group(P

关 键 词：运动 代谢型谷氨酸受体2/3 PD模型大鼠 纹状体 中等多棘神经元 

分 类 号：R742.5[医药卫生—神经病学与精神病学]