NR2B/CREB在人参皂苷Rb1调节甲基苯丙胺诱导大鼠条件位置偏爱中的作用  

Role of NR2B and CREB in ginsenoside Rb1 regulation of methamphetamine-induced conditioned place preference in rats

作　　者：杨根梦 何翠华 洪仕君 李娟 黄俭 沈宝玉 李媛媛 刘柳 曾晓锋 李利华 YANG Gen-meng;HE Cui-hua;HONG Shi-jun;LI Juan;HUANG Jian;SHEN Bao-yu;LI Yuan-yuan;LIU Liu;ZENG Xiao-feng;LI Li-hua(School of Forensic Medicine,Kunming Medical University,Kunming 650500,China;School of Basic Medicine,Kunming Medical University,Kunming 650500,China)

机构地区：[1]昆明医科大学法医学院,云南昆明650500 [2]昆明医科大学基础医学院,云南昆明650500

出　　处：《中国药理学通报》2020年第5期604-608,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81960340,81860332,81660310),云南省科技厅-昆明医科大学应用基础研究联合专项基金项目[No 2017FE467(-018)],昆明医科大学创新性实验计划项目(No 201940)。

摘　　要：目的研究人参皂苷Rb1(ginsenoside Rb1,Rb1)对甲基苯丙胺(methamphetamine,METH)诱导大鼠条件位置偏爱(conditioned place preference,CPP)的作用,并探讨NR2B/CREB在其中的作用。方法腹腔注射METH(2 mg·kg^-1)建立METH诱导大鼠CPP模型,0~3 d为适应阶段,4~13 d为实验阶段,每隔1 d给予METH(2 mg·kg^-1,i.p)或生理盐水(10 mg·kg^-1,i.p),Rb1(10 mg·kg^-1)或生理盐水提前1 h注射。灌注取脑后,在冰上分离海马组织,用Western blot检测各组海马组织中NR2B、CREB和p-CREB的表达情况。结果成功建立了METH诱导大鼠CPP模型。提前注射Rb1后,与METH组相比,大鼠停留在伴药箱的时间明显减少。Western blot结果显示:与对照组相比,METH可诱导大鼠海马组织中NR2B、p-CREB的表达水平和p-CREB/CREB比值明显升高,而CREB的,表达水平差异无显著性。Rb1(10 mg·kg^-1)干预后,与METH组相比,海马组织中NR2B,p-CREB的表达水平和p-CREB/CREB比值有所下降,而CREB的表达水平差异无显著性。结论METH可诱导大鼠CPP;Rb1通过调节NR2B和p-CREB对METH诱导大鼠CPP具有抑制作用。Aim To study the effect of ginsenoside Rb1 on methamphetamine-induced CPP in rats and to explore the role of NR2B/CREB in it.Methods METH(2 mg·kg^-1,i.p)was administered to estab-lish METH-induced CPP model in rats.0~3 d was the adaptation stage and 4~13 d was the experimental stage.METH(2 mg·kg^-1,i.p)or saline(10 mg·kg^-1,i.p)was injected every other day.Rb1(10 mg·kg^-1,i.p)or saline was pre-injected 1h before injection of METH or saline.After perfusion,the hippocampus was isolated from brain on ice,and the expression levels of NR2B,CREB and p-CREB were detected by Western blot.Results The animal model of METH-induced CPP was successfully established.The rats were pretreated with Rb1(10 mg·kg^-1)for 1 h,and the time that the rats stayed in drug-paired was significantly reduced compared with METH group.Western blot results showed that NR2B,p-CREB and p-CREB/CREB significantly increased in METH group and without altering CREB expression levels compared with control group.However,after pre-treated with Rb1,the expression levels of NR2B,p-CREB and p-CREB/CREB decreased compared with METH group.Conclusions METH can significantly induce CPP in rats.Rb1 may inhibit METH-induced CPP in rats by regulating NR2B and p-CREB.

关 键 词：甲基苯丙胺 人参皂苷RB1 条件位置偏爱 NR2B CREB 神经毒性作用 

分 类 号：R-332[医药卫生] R284.1