利扎曲普坦对偏头痛大鼠三叉神经节降钙素基因相关肽和脑啡肽原及缩胆囊肽基因表达的影响  

Effects of rizatriptan on calcitonin gene-related peptide, proenkephalin and cholecystokinin mRNA expressions in the trigeminal ganglia of a rat migraine model

作　　者：姚刚[1] 郝婷婷[2] 于挺敏[1] 

机构地区：[1]吉林大学第二医院神经内科,长春130041 [2]吉林大学第二医院核医学科,长春130041

出　　处：《中华神经科杂志》2014年第9期638-642,共5页Chinese Journal of Neurology

基　　金：吉林省卫生厅青年科研课题（2013Q020）;吉林大学白求恩青年科研基金项目（2013206044）

摘　　要：目的 观察利扎曲普坦对偏头痛大鼠三叉神经节降钙素基因相关肽（CGRP）、脑啡肽原和缩胆囊肽基因表达的影响,探讨曲普坦类药物对偏头痛发作时三叉神经节功能的干预作用.方法 将24只健康Wistar大鼠按随机区组法分为4组：A组：对照组,B组：偏头痛组,C组：利扎曲普坦对照组,D组：利扎曲普坦治疗组.利扎曲普坦给药组（C、D组）大鼠给予利扎曲普坦1mg·kg^-1·d^-1灌胃,A组和B组大鼠给予生理盐水2 ml/d灌胃.上述处理7d后,B、D组大鼠制备硝酸甘油型偏头痛动物模型,造模2h留取三叉神经节标本,用实时定量PCR检测其CGRP、脑啡肽原和缩胆囊肽mRNA表达.结果 A、B、C、D各组大鼠三叉神经节每200纳克总RNA中CGRP mRNA拷贝数（×10 7）分别为：0.05±0.01、1.30±0.52、0.23 ±0.12、0.43 ±0.33;脑啡肽原mRNA拷贝数（×103）分别为：3.30±1.65、0.34±0.14、3.91±2.44、0.71±0.13.B组大鼠三叉神经节CGRP mRNA拷贝数明显高于A组（q =7.854,P＜0.05）,D组大鼠三叉神经节CGRP mRNA拷贝数明显低于B组（q =5.458,P＜0.05）;B组大鼠三叉神经节脑啡肽原mRNA拷贝数明显低于A组（q =4.478,P＜0.05）;D组大鼠三叉神经节脑啡肽原mRNA拷贝数明显低于C组（q=4.838,P＜0.05）;各组大鼠三叉神经节缩胆囊肽mRNA表达差异无统计学意义.结论 利扎曲普坦可以抑制偏头痛发作时三叉神经节CGRP的过度表达,进而减弱三叉神经血管系统的激活,发挥治疗偏头痛的作用;偏头痛发作时三叉神经节脑啡肽原的基因表达明显减少,使得偏头痛发作时三叉神经节内脑啡肽减少,减弱脑啡肽的镇痛效应,利于头痛的持续.Objective This study assesses the influence of rizatriptan on calcitonin gene-related peptide （CGRP）,proenkephalin （PENK） and cholecystokinin （CCK） mRNA expressions in the trigeminal ganglia of a rat migraine model and investigates the possible mechanisms by which triptans treat migraine.Methods A total of 24 rats were randomly divided into four groups：normal control group （A）,migraine model group（B）,rizatriptan control group （C） and rizatriptan treatment group（D）.Groups C and D were intragastrically perfused with rizatriptan,1 mg/kg per day.After 7 days,nitroglycerin was subcutaneously injected into the buttocks of the groups B and D to induce migraine.Two hours after nitroglycerin injection,the trigeminal ganglia was isolated.CGRP,PENK and CCK mRNA expressions in the trigeminal ganglia were determined using SYBR Green Ⅰ real-time quantitative PCR.Results The copy number of CGRP mRNA （× 107） in 200 ng total RNA of each group was 0.05 ±0.01,1.30 ±0.52,0.23 ±0.12,0.43 ±0.33 ; The copy number of PENK mRNA （× 103） in 200 ng total RNA of each group was 3.30 ± 1.65,0.34 ±0.14,3.91 ± 2.44,0.71 ± 0.13.The copy number of CGRP mRNA in the trigeminal ganglia of group B was significantly higher than that of group A （q =7.854,P ＜ 0.05） ; CGRP mRNA expressions were significantly lower in the trigeminal ganglia of rats in group D compared with group B （q =5.458,P ＜0.05）.Compared with group A,PENK mRNA expressions in the trigeminal ganglia of rats were significantly lower in group B （q =4.478,P ＜ 0.05）.PENK mRNA expressions were significantly higher in trigeminal ganglia of rats in group C compared with group D （q =4.838,P ＜ 0.05）.CCK mRNA expression in trigeminal ganglia of rats was similar among groups.Conelusions Rizatriptan can decrease the expressions of CGRP in the trigeminal ganglia of the migraine rats and exhibits neurogenic inflammation triggered by CGRP.PENK expressions decrease in the trigeminal ganglia of the migraine rats,weaken the analgesi

关 键 词：偏头痛 三唑类 色胺类 三叉神经节 降钙素基因相关肽 脑啡肽类 蛋白质前体 胆囊收缩素 

分 类 号：R747.2[医药卫生—神经病学与精神病学]