G蛋白耦联受体激酶2在MPTP诱导的PD模型小鼠纹状体中的作用机制  

Increased expression of G protein-coupled receptor kinase 2 in the striatum of MPTP-induced PD model mice

作　　者：周畅 王埮[1,3] 许叶 赵振强 张海英[2,3] 马媛媛 陈志斌[1,2,3] ZHOU Chang;WANG Tan;XU Ye(Department of Neurology,the First Affiliated Hospital of Hainan Medical University,Haikou 570102,Hainan,China)

机构地区：[1]海南医学院第一附属医院神经内科,海南海口570102 [2]海南医学院 [3]海南热带脑科学研究与转化重点实验室

出　　处：《中国老年学杂志》2023年第19期4765-4769,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金地区科学项目(81860243);海南医学院第一附属医院青年培育基金(HYYFYPY202107);海南省临床医学中心建设项目。

摘　　要：目的 探究G蛋白耦联受体激酶(GRK)2在帕金森病(PD)小鼠纹状体中的作用机制。方法 选用C57BL/J雄性8周龄小鼠,随机分为对照组和模型组;对照组腹腔注射0.2 ml生理盐水,模型组腹腔注射30 mg/kg的1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP),2次/w,共5 w。35 d后对两组进行爬杆实验和旷场实验检测。行为学检测后,小鼠麻醉后眼球取血、取脑,运用酶联免疫吸附试验(ELISA)及免疫组化检测血清和中脑酪氨酸羟化酶(TH)表达,Western印迹和免疫组化检测纹状体GRK2和多巴胺2受体(D2R)表达。结果 在旷场实验中,MPTP干预后模型组自发活动总距离、穿越中心格次数和距离比对照组明显减少(均P<0.001)。在爬杆实验中,模型组爬杆时间比对照组明显延长(P<0.001)。ELISA及免疫组化显示,模型组血清和中脑TH值较对照组明显减少(P<0.001)。Western印迹和免疫组化提示,与对照组相比,纹状体D2R表达显著减少,而CRK2表达显著升高(P<0.05)。结论 GRK2可能通过D2R参与调控PD的症状,针对GRK2是潜在的PD治疗靶点。Objective To explore the changes of G protein-coupled receptor kinase(GRK)2 in the striatum of Parkinson's disease(PD)mice.Methods C57BL/J male 8-week-old mice were randomly divided into control group and model group.The control group were intraperitoneally injected 0.2 ml normal saline,the model group was intraperitoneally injected 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP),twice a week for a total of 5 w.After 35 d,two groups were tested by pole test and open field experiment.After behavioral tests,the mice were anesthetized to take blood from the eyeball and brain.Enzyme-linked immunosorbent assay(ELISA)and immunohistochemistry were used to detect the tyrosine hydroxylase(TH)expression in serum and midbrain.Western blot and immunohistochemistry were used to detect the expressions of GRK2 and dopamine 2 receptor(D2R)in the striatum.Results In the open field experiment,the total distance of spontaneous activity,the time passed through the center and the distance of the model group were significantly less than those of the control group after MPTP intervention(All P<0.001).In the pole test,the climbing time of the model group was significantly longer than that of the control group(P<0.001).The ELISA and immunohistochemistry results showed that the TH content of model group in serum and midbrain were significantly reduced than those in the control group(P<0.001).Western blot and immunohistochemistry indicated that,compared with control group,the expression of D2R in the striatum was significantly decreased,while the expression of GRK2 was significantly increased(P<0.05).Conclusions GRK2 might be involved in regulating the symptoms of PD through D2R,making it a potential target for the treatment of PD.

关 键 词：帕金森病 多巴胺2受体 G蛋白耦联受体激酶2 

分 类 号：R742[医药卫生—神经病学与精神病学]