下调PTEN基因对偏头痛大鼠三叉神经节CREB的调节作用  

Down-Regulation of PTEN Induced The Modulation of CREB in Trigeminal Ganglia of Migraine Rats

作　　者：桂蓓[1] 申崇标[1] 陈力学[1] 周冀英[1] 谭戈[1] 

机构地区：[1]重庆医科大学附属第一医院实验研究中心重庆市神经病学重点实验室,重庆400016

出　　处：《生物物理学报》2010年第9期805-813,共9页Acta Biophysica Sinica

基　　金：重庆市科委自然科学基金项目(CSTC2007BB5287);重医一院院内医学科学基金项目(YXJJ2009-15)~~

摘　　要：本研究利用RNAi重组腺病毒(AdR-siPTEN)下调偏头痛大鼠三叉神经节的PTEN(phosphatase and tensin homolog deleted on chromosome ten)基因,探讨其对偏头痛大鼠行为学的影响,以及经Akt(serine-threonine kinase)信号途径对CREB(cAMP responseelement-binding protein)的调控情况。实验采用健康雄性SD大鼠,随机分为假手术组(Sham)、硝酸甘油模型组(GTN)、Ad-RFP非特异siRNA处理空载体对照组(Vehicle+GTN)、AdR-siPTEN下调组(AdR-siPTEN+GTN)。用AdR-siPTEN重组腺病毒对大鼠进行预处理,然后通过硝酸甘油(glyceryl trinitrate,GTN)法建立大鼠偏头痛模型,进行大鼠挠头和爬笼次数的检测,并用RT-PCR和Western-blot法进行相关基因的mRNA和蛋白检测。结果表明,当PTEN基因表达下调时,有效缓解了偏头痛导致的挠头和爬笼行为,并激活Akt信号途径,增加其下游作用因子CREB的表达,进而可能经"PTEN/Akt/CREB"信号通路影响神经突触可塑性,参与了偏头痛的发病机制。The aim of the present study is to investigat whether down-regulation of PTEN（phosphatase and tensin homolog deleted on chromosome ten） by AdR-siPTEN recombinant adenovirus affected the behavior of migraine rats and regulated CREB（cAMP response element-binding protein） in trigeminal ganglia of migraine rats,involving in Akt（serine-threonine kinase） signaling pathway.The adult male SD rats were randomly assigned to four groups：Sham group、GTN group、Vehicle＋GTN group、AdR-siPTEN＋GTN group.Meanwhile,the rats were pretreated by AdR-siPTEN recombinant adenovirus,made GTN migraine models,and then submitted to behavioral testing of the rats to scratch their heads and climb hutch.The expression of related gene mRNA and proteins in rats trigeminal ganglia were detected by RT-PCR and Western-blot methods.The results showed that down-regulation of PTEN alleviated the migraine behavior that the rats scratched their heads and climbed hutch,activated Akt gene and increased the expression of the downstream factor CREB,furthermore affected the synaptic plasticity involving in the pathogenesis of migraine through PTEN /Akt /CREB signaling pathway in trigeminal ganglia of migraine rats.

关 键 词：PTEN CREB 偏头痛 三叉神经节 

分 类 号：R74[医药卫生—神经病学与精神病学]