下调PTEN基因对偏头痛大鼠三叉神经节NMDAR1和一氧化氮的影响  

EFFECTS OF PTEN GENE DOWN-REGULATION ON THE NMDAR1 EXPRESSION AND THE NITRIC OXIDE PRODUCTION IN MIGRAINE RATS

作　　者：冉丽[1] 申崇标[1] 陈力学[1] 谭戈[1] 桂蓓[1] 周冀英[1] 张和[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：《中国疼痛医学杂志》2012年第3期163-168,共6页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金(NO.81070886);重庆市教委科研资助项目(KJ100319);重庆市卫生局医学科研资助项目(2009-2-357)

摘　　要：目的:利用RNAi重组腺病毒下调第10号染色体同源丢失性磷酸酶张力蛋白基因(phosphata-se and tensin homology deleted on chromosome ten,PTEN)的表达,探讨PTEN基因是否参与偏头痛的病理过程及其对三叉神经节内N-甲基-D-天冬氨酸受体1亚基(N-methyl-D-aspartate receptor1,NMDAR1,简写NR1)和一氧化氮(nitric oxide,NO)的影响。方法:SD大鼠分成4组:假手术组(Sham组,n=12);硝酸甘油模型组(NTG组,n=12);PTEN基因下调组(AdR-siPTEN组,n=12);Ad-RFP非特异siRNA处理空载体对照组(Ad-RFP组,n=12)。将重组腺病毒立体定向注射入大鼠三叉神经节内,一周后通过皮下注射NTG建立偏头痛大鼠模型,分别于NTG注射前及注射后15分钟、30分钟、1、2、4小时观察大鼠痛阈变化,同时检测各组大鼠三叉神经节NR1和NO的差异。结果 :AdR-siPTEN腺病毒可下调三叉神经节PTEN基因的表达。与Ad-RFP组相比,AdR-siPTEN组的偏头痛大鼠痛阈明显增高,并且三叉神经节内NR1表达及NO合成明显减少。结论 :PTEN基因参与调节偏头痛的病理过程,下调PTEN基因可减轻NTG诱导的偏头痛大鼠模型对机械性刺激的反应,其机制可能是下调PTEN引起NR1表达量减低,继而引起NO含量降低所致。Objective： To employ the recombinant adenovirus AdR-siPTEN to knock down the gene of NMDA receptor NR1 subunit, to examine whether PTEN can modulate the pathological mechanism of migraine. Methods： Sprague-Dawley rats were randomly divided into 4 groups： Sham group （n = 12）; NTG group （n = 12）; AdR-siPTEN group （n = 12）; Ad-RFP group （n = 12）. One week after intraparenchymal administration of AdR-siPTEN into trigeminal ganglion, NTG was injected subcutaneously. The mechanic- al nociceptive thresholds before and at 15 rain, 30 rain, 1 h, 2 h and 4 h after NTG was evaluated, The change of NR1 expression and NO production of trigeminal ganglion were investigated. Results： The PTEN gene of trigeminal ganglion was down-regulated by the localized injection of AdR-siPTEN, which significantly increased the mechanical nociceptive thresholds and attenuated the NR1 expression and NO production of trigeminal ganglion in NTG-induced rats. Conclusion： PTEN may modulate the pathological mechanism of migraine. The PTEN gene down-regulation can reduce NTG-induced mechanical hypersensitivity. The mechanism related to the decreased NR1 expression and NO production.

关 键 词：偏头痛 第10号染色体同源丢失性磷酸酶张力蛋白基因 N-甲基-D-天门冬氨酸受体1亚基 一氧化氮 

分 类 号：R747.2[医药卫生—神经病学与精神病学]