摘要
目的：探讨神经病理性疼痛（neuropathic pain,NP）引起的成年大鼠的空间记忆障碍与内侧前额叶（medial prefrontal cortex,mPFC） NMDA受体NR2B亚基表达的关系.方法：选择健康的Wiser雄性大鼠50只,随机分为5组（每组10只）,分别为假手术组（sham operated group,SO组）,神经病理性疼痛模型组（neuropathic pain group,NP组）,生理盐水组（NS组）,Ro25-6981组（Ro组）和CX546组（CX组）.其中,NS组、Ro组和CX组是在NP模型基础上分别在mPFC区注射生理盐水、Ro25-6981和CX546.采用单侧坐骨神经主干慢性压迫法（chronic constriction injury,CCI）制备NP模型.SO组和NP组分别于术后第7d、14d、21 d和28 d测量机械缩足阈（mechanical withdrawalthreshold,MWT）和热缩足潜伏期（thermal withdrawal latency,TWL）.术后第21-28 d,进行八臂迷宫实验.术后第24 d,利用立体脑定位仪将生理盐水、Ro25-6981或CX546分别注射到mPFC,制备成NS组、Ro组或CX组动物模型.迷宫实验完成后立即处死大鼠,通过RT-PCR、免疫荧光和Western Blotting方法测定内侧前额叶的NR2B亚基mRNA和蛋白表达水平.结果：与SO组比较,NP组的MWT和TWL降低（P＜0.05）.与SO组比较,NP组的空间记忆功能明显减退（P＜0.05）.与NS组比较,Ro组的空间记忆功能明显减退（P＜0.05）,CX组的空间记忆功能明显改善（P＜ 0.01）.与SO组比较,NP组与NS组的NR2B亚基mRNA和蛋白表达均明显降低（P＜0.05）.与NS组比较,Ro组的mRNA和蛋白表达明显降低（P＜0.05）,而CX组的mRNA和蛋白表达明显升高（P＜0.01）.结论：NP所致空间记忆障碍可能与mPFC区的NR2B亚基下调表达有关.
Objective：To evaluate the relationship of spatial memory impairment induced by neuropathic pain （NP） and expression of NMDA receptor NR2B subtype in medial prefrontal cortex （mPFC） in adult rats.Methods：50 healthy male Wistar rats were randomly divided into 5 groups （n =10）：sham operated group （SO group）,neuropathic pain group （NP group）,the normal saline group （NS group）,Ro25-6981 group （Ro group） and CX546 group （CX group）.NS,Ro and CX groups were based on NP group.The NP model of the chronic constriction injury of the sciatic nerve stem was used.Mechanical withdrawal threshold （MWT） and thermal withdrawal latency （TWL） were measured in SO and NP groups 7^th,14^th,21^st and 28^th day after injury.21^st- 28^th day after injury eight-arm radial maze task was detected to evaluate the spatial memory.24th day after injury normal saline,Ro25-6981 or CX546 was injected in mPFC of NP group by stereotaxic apparatus to prepare NS group,Ro group or CX group.Once maze task was finished,rats were killed to measure the expression of NR2B subtype mRNA and protein in mPFC by RT-PCR,immunofluorescence and Western Blotting methods.Results：Compared with SO group,MWT and TWL in NP group were both reduced （P 〈 0.05）.Compared with SO group,spatial memory in NP group was declined significantly （P 〈 0.05）.Compared with NS group,spatial memory in Ro group was declined significantly （P 〈 0.05）,CX group was improved significantly （P 〈 0.01）.Compared with SO group,expression of NR2B subunit mRNA and protein in NP group and NS group was reduced significantly （P 〈 0.05）.Compared with NS group,expression ofNR2B mRNA and protein in Ro group was reduced significantly （P 〈 0.05）,CX group was increased significantly （P 〈 0.01）.Conclusion：Spatial memory impairment induced by NP may be associated with the low expression of NR2B subunit in mPFC.
出处
《中国疼痛医学杂志》
CAS
CSCD
2015年第1期21-27,共7页
Chinese Journal of Pain Medicine
基金
国家自然科学基金(81241041)
山东省自然科学基金(ZR2012HM077)
山东省高等学校科技计划项目(J12LL01)
山东省医药卫生科技发展计划项目(2011HZ113)
潍坊医学院前沿探索重点研究基金(K11TS1002)
