同型半胱氨酸与N-甲基-D-天冬氨酸受体的研究进展

同型半胱氨酸(homocysteine,Hcy)是心血管疾病的独立危险因子,作用机制涉及损伤血管功能、活化炎症细胞和血小板、促进凝血及心肌肥大等方面。N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体是兴奋性氨基酸受体的一种亚型,传统观点认为其主要分布在中枢神经系统,在神经元回路的形成及学习、记忆过程中起关键作用,并与神经退行性疾病密切相关。近年来,NMDA受体在心血管疾病中的作用得到人们的关注。现就NMDA受体在Hcy致心血管细胞功能损伤中的作用方面的研究进展作一综述。     

谷氨酸及其N-甲基-D-天冬氨酸受体在肺损伤中的作用

谷氨酸是哺乳动物中枢神经系统兴奋性氨基酸神经递质,N-甲基-D-天冬氨酸（N—methyl—D-aspartate,NMDA）受体是谷氨酸重要的离子型受体。多种外周非神经组织也发现NMDA受体在维持组织正常的生理功能、参与组织细胞的损伤与修复等方面发挥重要作用。近年来发现在肺组织同样存在NMDA受体的表达,后者参与多种肺部疾病的发生与发展。     

抗N-甲基-D-天冬氨酸受体脑炎精神行为异常的研究

摘要 抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎是自身免疫性脑炎(AE)的最主要类型,精神行为异常是其常见、有时甚至是首发的临床症状,会造成患者首诊于精神科,极易导致漏诊、误诊和误治。因此,正确认识和识别抗NMDAR脑炎的精神行为异常有助于及早明确诊断、及时给予恰当的治疗、进而改善患者的预后。本文拟对抗NMDAR脑炎精神行为异常的发病机制、临床特点、辅助检查、治疗及预后等进行综述,为提高临床医生对抗NMDAR脑炎精神行为异常的认识和识别能力而提供帮助。     

脑梗死患者血小板N-甲基-D-天冬氨酸受体表达与阿司匹林抵抗的相关性研究

目的探讨脑梗死患者血小板N-甲基-D-天冬氨酸(NMDA)受体表达与阿司匹林抵抗(AR)的相关性。方法选择2011年8月—2013年7月在我院神经内科住院的脑梗死患者45例为脑梗死组,同期在我院体检中心体检健康者40例为对照组。脑梗死患者确诊后即开始规律服用阿司匹林(100 mg/d),检测两组受检者NMDA受体表达水平和血小板聚集率。结果对照组受检者NMDA受体相对表达量为(0.11±0.07),低于脑梗死组-治疗前患者的(0.32±0.12)(P0.001),脑梗死组-治疗前患者NMDA受体相对表达量低于脑梗死组-治疗后患者的(0.69±0.15)(P0.001)。对照组受检者血小板聚集率为(32.38±11.38)%,脑梗死组-治疗后患者为(43.81±14.40)%,均低于脑梗死组-治疗前患者的(57.00±18.96)%。Spearman相关分析结果显示,对照组受检者、脑梗死组-治疗前患者、脑梗死组-治疗后患者血小板NMDA受体相对表达量与血小板聚集率均无直线相关性(P0.05)。结论脑梗死患者血小板NMDA受体表达水平升高,阿司匹林可上调脑梗死患者血小板NMDA受体的表达,NMDA受体表达增加可能是脑梗死患者发生AR的重要原因。     

抗N-甲基-D-天冬氨酸受体抗体脑炎的研究进展

自身免疫性脑炎指机体自身免疫系统针对中枢神经系统抗原产生的抗原抗体反应,从而引起中枢神经系统损伤的一类疾病。其病因可能是由于某些自身抗体、活性细胞或相关因子与中枢神经系统神经元表面的蛋白等相互作用。主要分为特异性抗原抗体相关性脑炎和非特异性抗原抗体相关性脑炎两类,其中非特异抗原抗体相关性脑炎（如急性播散性脑脊髓炎）临床较多见。     

抗N-甲基-D-天冬氨酸受体脑炎病人临床和脑电图特点分析

目的探讨抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎临床特点及脑电图电生理特征。方法选取2018年1月—2019年1月首都医科大学宣武医院神经内科收治的56例抗NMDAR脑炎病人,收集病人一般情况、临床特点、实验室及影像学检查、治疗及预后情况。结果56例抗NMDAR脑炎病人男女比例为3∶5,中位年龄为21.5岁。30例(53.57%)病人有前驱感染病史,以头痛最为常见。首发症状以癫痫起病22例(39.29%),精神行为异常29例(51.79%)。随着疾病的发展,43例(76.79%)出现癫痫发作,以局灶性发作继发全面强直阵挛最为常见;52例(92.86%)发展至精神行为异常;29例(51.79%)出现记忆力下降。16例(28.57%)出现不自主运动;8例(14.29%)病人出现中枢性低通气。脑脊液白细胞计数为14×10⁶/L,其中57.14%病人高于8×10⁶/L,12.5%的病人蛋白水平高于正常。脑电图分析发现中度异常32例(57.14%),重度异常20例(35.71%),其中出现极度δ刷5例;癫痫样放电共13例(23.21%)。头颅MRI检查脑炎性改变24例(42.86%)。3例(5.36%)病人经肿瘤筛查发现畸胎瘤。所有病人均接受一线免疫治疗,48例(85.71%)病人在治疗后症状得到不同程度的改善。经随访12例(21.43%)病人出现病情复发,其余病人遗留轻微症状或症状完全消失。结论抗NMDAR脑炎以青年女性较为常见,临床症状多样,具有前驱感染症状。脑脊液可提示炎症改变,脑电图对抗NMDAR脑炎具有重要意义,早期及时的免疫治疗可有效改善病人预后。     

老年人抗N-甲基-D-天冬氨酸受体脑炎五例

<正>抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎是与自身抗体介导的突触功能障碍有关的自身免疫性脑炎。该病是备受关注的边缘性脑炎的一种,多见于育龄期女性和儿童,老年、男性则相对少见~([1])。本研究回顾性分析5例老年抗NMDAR脑炎患者的临床资料。1临床资料收集2015年1月～2018年9月在赣南医学院第一附属医院确诊的抗NMDAR脑炎患者5例,男性4例,女性1例,年龄60～70岁,平均年龄63.4岁。所有患者诊断和治疗均按2017年中国自身免疫性脑炎诊治专家共识及2016年自身免疫性脑炎诊治指南[2-3]。病例1男性,70岁;病例2男     

白芍对斜视性弱视模型猫视皮质N-甲基-D-天冬氨酸受体1表达的影响

目的观察白芍(RPA)对斜视性弱视模型猫的治疗作用及其对视皮质N-甲基-D-天冬氨酸受体(NMDAR)1表达的影响。方法将18只幼猫随机分为正常组、模型组、RPA组,每组6只,构建斜视性弱视猫模型。RPA组灌胃RPA 30 d,正常组和模型组注射等体积生理盐水。给药结束后观察扫描视觉诱发电位(SVEP)视力、图形视觉诱发电位(PVEP)视力、17区的眼驱动细胞数等相关指标,并通过实时定量聚合酶链反应检测眼左右侧17区、21a区NMDAR1的水平。结果 RPA对斜视性弱视模型猫的治疗有显著作用,可提高斜视性弱视模型猫视皮质NMDAR1的表达。结论 RPA可以提高斜视性弱视模型猫视皮质的神经元突触兴奋性,逆转弱视的形成,达到治疗弱视的目的,其作用可能是通过提高斜视性弱视模型猫视皮质NMDAR1的表达来实现的。     

雌激素对AD大鼠模型N-甲基-D-天冬氨酸受体表达的影响

目的 探讨雌激素对阿尔茨海默病 (AD) 大鼠模型的学习记忆能力及N-甲基-D天冬氨酸受体-1 (NMDAR1) 表达的影响.方法 大鼠卵巢切除术(OVX)后给予雌激素替代治疗(ERT),然后采用Aβ1～40,1 μl(10 μg/μl) 立体定位单侧海马内注射建立AD动物模型,通过水迷宫实验检测动物模型的学习、记忆能力;免疫组化检测NMDAR1的蛋白表达情况.结果 ERT组AD动物模型的水迷宫逃避潜伏期较OVX组明显缩短(P<0.05);同时ERT组AD动物模型的海马CA1、CA3区的NMDAR1的蛋白表达上调(P<0.05).结论 雌激素可以改善AD动物模型的认知功能;其神经保护作用可能与上调NMDAR1的蛋白表达有关.     

N-甲基-D-天冬氨酸受体1在一过性肠道感染大鼠内脏高敏感形成中的意义

目的 研究N-甲基-D-天冬氨酸受体1(NMDA-R1)在SD大鼠—过性肠道感染旋毛虫后形成的内脏高敏感中的作用.方法 40只SD大鼠均分为健康对照组、内脏高敏感组、0.9％氯化钠溶液组、MK-801组,其中内脏高敏感组、0.9％氯化钠溶液组和MK 801组分别予旋毛虫感染造模.8周后,0.9％氯化钠溶液组和MK-801组分别予0.9％氯化钠溶液和NMDA-R1拮抗剂MK-801.观察各组在20、40、60和80 mm Hg(1 mm Hg=0.133 kPa)结直肠扩张压力下腹壁肌电活动反应.测定腹壁肌电活动后,取大鼠结肠标本,采用Western印迹检测NMDA-R1蛋白水平的表达.统计学处理采用Bivariate相关分析和LSD检验.结果 健康对照组、内脏高敏感组、0.9％氯化钠溶液组和MK-801组腹壁肌电图曲线下面积(AUC)与扩张压力之间均有相关性(r=0.823、0.618、0.913、0.889,均P＜0.01).在20、40、60和80 mm Hg扩张压力下,MK-801组与内脏高敏感组AUC间差异均有统计学意义(LSD检验,P值均＜0.05),MK-801组AUC均小于健康对照组,但只在80 mm Hg扩张压力下差异有统计学意义(LSD检验,P=0.029).MK-801组NMDA-R1蛋白积分吸光度相对值为1.238±0.210,较内脏高敏感组(2.231±0.450)和0.9％氯化钠溶液组(2.104±0.220)均显著降低(LSD检验,P=0.025和0.046),内脏高敏感组NMDA-R1蛋白积分吸光度相对值和0.9％氯化钠溶液组较健康对照组显著升高(1SD检验,P=0.007和0.014).结论 内脏高敏感的形成与突触后NMDA-R1的高表达密切相关,抑制肠道神经系统中NMDA-R1的表达可调节内脏高敏感性.     

N-甲基-D-天冬氨酸受体NR2B亚基与神经元凋亡

神经元凋亡是缺血性卒中神经元死亡的重要形式之一.在神经元凋亡过程中,民N-甲基-D-天冬氨酸(N-methyl-D-aspartate,NMDA)受体介导的兴奋性氨基酸毒性起着重要作用,是神经元凋亡的启动者和执行者.NR2B是该受体的主要调节亚基,其跨膜片段M2是一个面向胞质向膜内反折的膜襻区,形成离子通道的内壁,决定了NMDA受体离子通道对ca2+的通透性.谷氨酸主要通过钙超载介导细胞损伤,因此,NR2B亚基在缺血性卒中神经元凋亡中起着至关重要的作用.     

美金刚对血管性痴呆大鼠海马N-甲基-D-天冬氨酸-2B受体的影响

目的观察经美金刚治疗的血管性痴呆(VaD)大鼠海马N-甲基D-天冬氨酸-2B受体(NMDAR-2B)的变化,并探讨其在VaD中的作用机制。方法采用永久性结扎双侧颈总动脉方法制备VaD大鼠模型,将128只Wistar大鼠随机分为假手术组、VaD模型组和美金刚高、低剂量治疗组,每组32只,各组分别于术后4、8、12、16周处死8只大鼠。用Morris水迷宫衡量大鼠学习记忆水平,用免疫组织化学法检测大鼠海马NMDAR-2B的表达。结果随缺血时间延长,VaD模型组大鼠的学习记忆能力下降,与假手术组比较有显著性差异(P<0.01);NMDAR-2B的表达在缺血4周时明显高于假手术组(P<0.01),此后逐渐减少,并显著低于假手术组(P<0.01),缺血16周时表达最少。学习记忆水平及NMDAR-2B的表达美金刚高、低剂量治疗组在缺血4周时与假手术组比较无显著性差异,在缺血8、12、16周时,美金刚高剂量治疗组较VaD模型组显著好转但仍低于假手术组(P<0.01,P<0.05),美金刚低剂量治疗组与模型组无显著差异但明显低于假手术组(P<0.05,P<0.01)。结论VaD大鼠学习记忆的改变与海马NMDAR-2B变化相关,可用适量的美金刚对NMDAR-2B调节以改善VaD大鼠认知功能。     

N-甲基-D-天门冬氨酸受体和活性氧对血管平滑肌细胞活性的影响

目的研究N-甲基-D-天门冬氨酸(N-methy-D-aspartate,NMDA)受体和活性氧(reactive oxygen species,ROS)是否参与同型半胱氨酸(homocysteine,Hcy)诱导血管平滑肌细胞活性的增强。方法采用5-溴脱氧尿嘧啶(BrdU)合成实验观察细胞的增殖活性,Trans well方法观察细胞的迁移活性,二乙酰二氯氢化荧光素检测平滑肌细胞中ROS水平。结果随Hcy浓度增加,Hcy诱导血管平滑肌细胞增殖、迁移活性增强,呈剂量依赖性,NMDA受体拮抗剂MK801、NAD(P)H氧化酶抑制剂二苯基碘(DPI)、自由基清除剂N-2酰半胱氨酸(NAC)能抑制Hcy诱导的增殖、迁移活性的增强。Hcy刺激后平滑肌细胞ROS水平升高作用能够被MK801、DPI、NAC抑制。结论ROS参与了Hcy诱导的血管平滑肌细胞增殖和迁移活性的增强,并且该途径是通过NMDA受体介导的。     

N-甲基-D-天冬氨酸受体2B基因(GRIN2B)启动子区多态性与散发性阿尔茨海默病的相关性分析

目的探讨中国北方汉族人群N-甲基-D-天冬氨酸受体2B(N-methyl-D-aspartate receptor2B,NR2B)基因GRIN2B启动子区变异与散发性阿尔茨海默病(sporadic Alzheimer′s disease,SAD)的关系。方法利用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法对中国北方汉族362例SAD患者和334名正常对照者进行GRIN2B启动子多态性及载脂蛋白E(ApoE)分型。结果中国北方汉族人群中GRIN2B启动子区存在-200T/G(rs1019385)、-421C/A(rs3764028)、-1447T/C(ENS10557853)和-1497G/A(rs12368476)多态性位点;-421C/A多态性在SAD和正常对照组中的基因型频率(P=0.029)和等位基因频率(P=0.010)差异显著;不携带ApoEε4的人群中-421C/A多态性的基因型频率(P=0.012)及等位基因频率(P=0.004)差异亦显著;所发现的4个多态性位点之间存在连锁不平衡关系,但其单体型分布在AD组和正常对照组中差异不显著。结论-421C/A多态性与AD发病有明显的相关性,在ApoEε4阴性的人群中这种相关性更为明显,-421C/A多态性可能独立于ApoEε4而影响SAD发病。     

同型半胱氨酸经由N-甲基-D-天冬氨酸受体-Cyclin D通路诱导血管平滑肌细胞增殖

目的探讨同型半胱氨酸可否经由N-甲基-D-天冬氨酸受体通路诱导血管平滑肌细胞增殖及其可能的终末靶分子。方法以同型半胱氨酸诱导血管平滑肌细胞增殖,并合用N-甲基-D-天门冬氨酸受体拮抗剂MK801以观察其对血管平滑肌细胞增殖的影响。应用MTT法检测血管平滑肌细胞增殖;流式细胞术测定细胞周期;逆转录聚合酶链反应检测Cyclin D1 mRNA的表达。结果同型半胱氨酸显著刺激血管平滑肌细胞增殖、促进血管平滑肌细胞从G0/G1向S期转换,并上调Cyclin D1 mRNA的表达。而N-甲基-D-天冬氨酸受体拮抗剂MK801同步抑制血管平滑肌细胞增殖及血管平滑肌细胞从G0/G1向S期转换,同时降低Cyclin D1 mRNA的表达,上述效应皆具明显的剂量-效应关系。结论同型半胱氨酸对血管平滑肌细胞的促增殖效应可能部分是通过N-甲基-D-天冬氨酸受体介导,并最终经由Cyclin D通路实现。     

帕金森病运动并发症发生机制中G蛋白偶联受体激酶6与N-甲基-D-天冬氨酸受体关系的研究

目的 研究G蛋白偶联受体激酶6(GRK6)在帕金森病(PD)运动并发症发生机制中与N-甲基-D-天冬氨酸(NMDA)受体的关系.方法 建立PD运动并发症大鼠模型,25只大鼠分为3组.异动症(LID)组10只,腹腔注射左旋多巴甲酯23 d;MK-801处理组10只,第23天左旋多巴甲酯注射前腹腔注射MK-801;PD组5只,腹腔注射0.2%维生素C液.另设假手术组5只为对照组.观察MK-801处理左旋多巴诱导的运动并发症模型大鼠的行为变化,并用免疫组织化学方法和Western印迹方法检测大鼠纹状体区GRK6蛋白的表达情况.结果 PD组大鼠长期使用左旋多巴后出现明显的异常不自主运动,与人类LID具有相似特征.免疫组化结果显示.PD组损伤侧纹状体区GRK6阳性细胞指数减少至(4.81±1.31)×103(P＜0.05),LID组损伤侧GRK6阳性细胞指数进一步减少至(3.23±0.41)×103(P＜0.01).MK-801组LID大鼠异常不自主运动评分减少,药效期延长,同时损伤侧纹状体区GRK6阳性细胞指数增多至(4.64±1.39)×103(P＜0.05).Western印迹法检测结果同免疫组化基本相符,PD组损毁侧/未损毁侧纹状体区GRK6含量比值为(83.7±2.1)%,LID组GRK6值降低为(76.8±2.2)%,而MK-801组GRK6值升高至(91.1±2.7)%(P＜0.01).结论 NMDA受体拮抗剂能逆转大鼠运动并发症的发生,其机制可能与GRK6增多,抑制了谷氨酸受体的过度活化有关.

Abstract：

Objective To investigate the relationship between G protein-coupled receptor kinase 6 (GRK6) and N-methyl-D-aspartate (NMDA) receptor in the mechanism study underlying motor complications in Parkinson's disease (PD).Methods The rat models (n= 25) of Parkinsonism related motor complications were established and were randomly divided into levodopa-induced dyskinesia (LID) group (n= 10,intraperitoneal injection of levodopa for 23 d),MK-801 treatment group (n= 10,intraperitoneal injection of MK-801 at day23 after intraperitoneal injection with levodopa for 22 days) and PD group (n= 5,intraperitoneal injection of vitamin C).Another 5 rats were served as controls (sham-operation group).The behavior changes of rats in MK-801 treatment group were observed,and the expression of GRK6 in the striate of rats was detected by immunohistochemistry and Western blot.Results After the chronic treatment with levodopa methyl ester,PD rats displayed abnormal involuntary movements,which was similar to levodopainduced dyskinesia in PD patients.Immunohistochemistry showed that GRK6-positive cells of lesion side were decreased in LID rats as compared with PD rats [(3.23±0.41 ) × 103 vs.(4.81 ± 1.31 ) ×103,P＜0.01].Rats in MK-801 treatment group displayed the decreased AIM scores and increased peak rotation,and the increased GRK6-positive cells of lesion side as compared with LID rats (P＜0.05).Western blot showed that the levels of GRK6 was 83.7% ±2.1% in PD group (presented as lesion side/unlesion side),76.8% ± 2.2% in LID group and 91.1% ± 2.7% in MK-801 treatment group (intergroups comparison:all P＜0.05).These results were in accordance with the results of immunohistochemistry.Conclusions Antagonist of NMDA receptor can be used to reduce the motor complications in rats.It may be due to increased GRK6 which inhibits the overactivation of glutamic acid receptors.     

帕金森病运动并发症发生机制中G蛋白偶联受体激酶6与N-甲基-D-天冬氨酸受体关系的研究

Objective To investigate the relationship between G protein-coupled receptor kinase 6 (GRK6) and N-methyl-D-aspartate (NMDA) receptor in the mechanism study underlying motor complications in Parkinson's disease (PD).Methods The rat models (n= 25) of Parkinsonism related motor complications were established and were randomly divided into levodopa-induced dyskinesia (LID) group (n= 10,intraperitoneal injection of levodopa for 23 d),MK-801 treatment group (n= 10,intraperitoneal injection of MK-801 at day23 after intraperitoneal injection with levodopa for 22 days) and PD group (n= 5,intraperitoneal injection of vitamin C).Another 5 rats were served as controls (sham-operation group).The behavior changes of rats in MK-801 treatment group were observed,and the expression of GRK6 in the striate of rats was detected by immunohistochemistry and Western blot.Results After the chronic treatment with levodopa methyl ester,PD rats displayed abnormal involuntary movements,which was similar to levodopainduced dyskinesia in PD patients.Immunohistochemistry showed that GRK6-positive cells of lesion side were decreased in LID rats as compared with PD rats [(3.23±0.41 ) × 103 vs.(4.81 ± 1.31 ) ×103,P＜0.01].Rats in MK-801 treatment group displayed the decreased AIM scores and increased peak rotation,and the increased GRK6-positive cells of lesion side as compared with LID rats (P＜0.05).Western blot showed that the levels of GRK6 was 83.7% ±2.1% in PD group (presented as lesion side/unlesion side),76.8% ± 2.2% in LID group and 91.1% ± 2.7% in MK-801 treatment group (intergroups comparison:all P＜0.05).These results were in accordance with the results of immunohistochemistry.Conclusions Antagonist of NMDA receptor can be used to reduce the motor complications in rats.It may be due to increased GRK6 which inhibits the overactivation of glutamic acid receptors.     

帕金森病运动并发症发生机制中G蛋白偶联受体激酶6与N-甲基-D-天冬氨酸受体关系的研究

Objective To investigate the relationship between G protein-coupled receptor kinase 6 (GRK6) and N-methyl-D-aspartate (NMDA) receptor in the mechanism study underlying motor complications in Parkinson's disease (PD).Methods The rat models (n= 25) of Parkinsonism related motor complications were established and were randomly divided into levodopa-induced dyskinesia (LID) group (n= 10,intraperitoneal injection of levodopa for 23 d),MK-801 treatment group (n= 10,intraperitoneal injection of MK-801 at day23 after intraperitoneal injection with levodopa for 22 days) and PD group (n= 5,intraperitoneal injection of vitamin C).Another 5 rats were served as controls (sham-operation group).The behavior changes of rats in MK-801 treatment group were observed,and the expression of GRK6 in the striate of rats was detected by immunohistochemistry and Western blot.Results After the chronic treatment with levodopa methyl ester,PD rats displayed abnormal involuntary movements,which was similar to levodopainduced dyskinesia in PD patients.Immunohistochemistry showed that GRK6-positive cells of lesion side were decreased in LID rats as compared with PD rats [(3.23±0.41 ) × 103 vs.(4.81 ± 1.31 ) ×103,P＜0.01].Rats in MK-801 treatment group displayed the decreased AIM scores and increased peak rotation,and the increased GRK6-positive cells of lesion side as compared with LID rats (P＜0.05).Western blot showed that the levels of GRK6 was 83.7% ±2.1% in PD group (presented as lesion side/unlesion side),76.8% ± 2.2% in LID group and 91.1% ± 2.7% in MK-801 treatment group (intergroups comparison:all P＜0.05).These results were in accordance with the results of immunohistochemistry.Conclusions Antagonist of NMDA receptor can be used to reduce the motor complications in rats.It may be due to increased GRK6 which inhibits the overactivation of glutamic acid receptors.     

帕金森病运动并发症发生机制中G蛋白偶联受体激酶6与N-甲基-D-天冬氨酸受体关系的研究

Objective To investigate the relationship between G protein-coupled receptor kinase 6 (GRK6) and N-methyl-D-aspartate (NMDA) receptor in the mechanism study underlying motor complications in Parkinson's disease (PD).Methods The rat models (n= 25) of Parkinsonism related motor complications were established and were randomly divided into levodopa-induced dyskinesia (LID) group (n= 10,intraperitoneal injection of levodopa for 23 d),MK-801 treatment group (n= 10,intraperitoneal injection of MK-801 at day23 after intraperitoneal injection with levodopa for 22 days) and PD group (n= 5,intraperitoneal injection of vitamin C).Another 5 rats were served as controls (sham-operation group).The behavior changes of rats in MK-801 treatment group were observed,and the expression of GRK6 in the striate of rats was detected by immunohistochemistry and Western blot.Results After the chronic treatment with levodopa methyl ester,PD rats displayed abnormal involuntary movements,which was similar to levodopainduced dyskinesia in PD patients.Immunohistochemistry showed that GRK6-positive cells of lesion side were decreased in LID rats as compared with PD rats [(3.23±0.41 ) × 103 vs.(4.81 ± 1.31 ) ×103,P＜0.01].Rats in MK-801 treatment group displayed the decreased AIM scores and increased peak rotation,and the increased GRK6-positive cells of lesion side as compared with LID rats (P＜0.05).Western blot showed that the levels of GRK6 was 83.7% ±2.1% in PD group (presented as lesion side/unlesion side),76.8% ± 2.2% in LID group and 91.1% ± 2.7% in MK-801 treatment group (intergroups comparison:all P＜0.05).These results were in accordance with the results of immunohistochemistry.Conclusions Antagonist of NMDA receptor can be used to reduce the motor complications in rats.It may be due to increased GRK6 which inhibits the overactivation of glutamic acid receptors.