RGS4过表达对甲基苯丙胺依赖大鼠纹状体mGluR5信号传导通路相关蛋白表达的影响  

Effect of RGS4 overexpression on related protein expression of mGluR5-mediated signaling pathway in methamphetamine-dependent rat striatum

作　　者：赵林波 隋念含 蒙国懿 洪仕君 李利华 邢豫明[4] 赵永娜 ZHAO Lin-bo;SUI Nian-han;MENG Guo-yi;HONG Shi-jun;LI Li-hua;XING Yu-ming;ZHAO Yong-na(School of Institute of Information,Yunnan University of Chinese Medicine,Kunming 650500,China;School of Pharmaceutical Sciences and Yunnan Key Lab of Pharmacology for Natural Product,Kunming Medical University,Kunming 650500,China;School of Forensic Medicine,Kunming Medical University,Kunming 650500,China;Key Lab of drug analysis and drug control technology of Yunnan Provincial Police Department,Kunming 650228,China)

机构地区：[1]云南中医药大学信息学院,云南昆明650500 [2]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500 [3]昆明医科大学法医学院,云南昆明650500 [4]云南省公安厅禁毒处毒品分析与禁毒技术公安部重点实验室,云南昆明650228

出　　处：《中国药理学通报》2019年第8期1115-1120,共6页Chinese Pharmacological Bulletin

基　　金：云南省应用基础研究计划联合专项基金资助项目(No2012FB023)

摘　　要：目的 通过建立大鼠甲基苯丙胺(METH)依赖条件位置偏爱模型(CPP),研究脑纹状体内G蛋白信号调节因子4(RGS4)过表达引起的代谢型谷氨酸受体5(mGluR5)信号传导通路相关蛋白表达变化,以及对大鼠CPP行为的影响。方法将大鼠随机分为正常组、生理盐水(NS)组、METH组、Ad5-RGS4-EGFP组、Ad5-EGFP组。正常组不做处理,其余各组脑纹状体分别立体定位注射磷酸盐缓冲液(PBS)、PBS、过表达腺病毒载体Ad5-RGS4-EGFP和阴性对照腺病毒载体Ad5-EGFP,分析各组大鼠CPP行为,Western blot检测脑纹状体内RGS4、mGluR5、Gαq、PLCβ1等蛋白的表达。结果 Ad5-RGS4-EGFP组CPP差值低于METH组和Ad5-EGFP组(P<0.05),高于NS组(P<0.05)。Ad5-RGS4-EGFP组RGS4蛋白表达均不同程度高于其余4组(P<0.05,P <0.01),mGluR5、Gαq表达低于METH组和Ad5-EGFP组(P<0.05),略高于正常组和NS组( P >0.05),PLCβ1表达略有变化,但差异无显著性。结论纹状体内RGS4过表达可明显缓解METH成瘾性大鼠CPP行为,机制可能与RGS4过表达后,负性调控mGluR5介导的Gαq及PLCβ1信号传导通路相关。Aim To investigate the effect of the regulator of G-protein signaling 4(RGS4) overexpression in rat striatum on the related protein expression of metabolic glutamate receptor 5(mGluR5) signaling pathway and the conditioned place preference(CPP) behavior in rats,by establishing the METH-dependent CPP model.Methods Rats were divided into five groups: normal,normal saline(NS),METH,Ad5-RGS4-EGFP and Ad5-EGFP group.Normal group was without any administration,while the striatum of the other groups were respectively stereotactic injected with phosphate buffer methamphetamine (METH)-depardent soline (PBS),PBS,overexpressed adenovirus vector Ad5-RGS4-EGFP and negative control adenovirus vector Ad5-EGFP.The CPP behavior of rats in each group was analyzed.The expression of RGS4,mGluR5,Gαq,PLC1 was measured in rat striatum tissue by Western blot.Results The difference of CPP in Ad5-RGS4-EGFP group decreased compared with that in METH group and Ad5-EGFP group(P<0.05),and increased compared with that in NS group(P<0.05).RGS4 expression in Ad5-RGS4-EGFP group increased compared with that in other groups(P<0.05,P <0.01),the expression levels of mGluR5,Gαq decreased compared with those in METH group and Ad5-EGFP group(P<0.05),while slightly increased compared with that in normal group and NS group( P >0.05).PLCβ1 expression changed with no significant difference.Conclusions RGS4 overexpression in striatum is able to alleviate the CPP behavior in METH-dependent rats,and its mechanism may be associated with the overexpression of RGS4 in METH-dependent rat striatum,which could down-regulate the mGluR5-mediated Gαq and PLCβ1 signaling pathway.

关 键 词：甲基苯丙胺 纹状体 条件位置偏爱 G蛋白信号调节因子4 代谢型谷氨酸受体5 G蛋白α亚单位蛋白q 磷脂酶C-β1 

分 类 号：R-332[医药卫生] R322.81