脊髓mTOR信号通路在大鼠神经病理性痛形成中的作用  

Role of mammlian target of rapamycin signaling pathway in spinal cord in development of neuropathic pain in rats

作　　者：彭志勇[1] 程智刚[2] 王喜梅[2] 王云姣[2] 杨文茜[2] 潘冰冰[2] 邢纪宾 郭曲练[2] 吴晓英[3] 

机构地区：[1]南方医科大学附属南海医院麻醉科, 广东省佛山市528200 [2] 中南大学湘雅医院麻醉科 [3] 中南大学湘雅医学院超微结构教研室

出　　处：《中华麻醉学杂志》2013年第12期1439-1442,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（30872427）

摘　　要：目的 评价脊髓哺乳动物雷帕霉素靶蛋白（mTOR）信号通路在大鼠神经病理性痛形成中的作用.方法 清洁级健康成年雄性SD大鼠20只,体重180 ～ 220 g,采用随机数字表法分为4组（n=5）：对照组（C组）、假手术组（S组）、神经病理性痛组（NP组）和雷帕霉素组（R组）.除C组外,各组大鼠均行鞘内置管术成功后观察3d.S组仅分离坐骨神经不结扎;NP组采用结扎坐骨神经的方法制备大鼠神经病理性痛模型;R组结扎坐骨神经后4h鞘内注射4％雷帕霉素10μl,连续3d.在结扎坐骨神经前1d和结扎后3、5和7d时测定机械痛阈,定量分析脊髓背角Ⅱ层神经元的细胞器和突触结构变化.结果 与C组和S组比较,NP组和R组结扎后5和7d时机械痛阈降低,总突触、棘突触、凹型突触、穿孔性突触密度及突触后致密区厚度、突触界面曲率增加（P＜ 0.05或0.01）;与NP组比较,R组结扎后5和7d时机械痛阈升高,总突触、棘突触、凹型突触、穿孔性突触密度及突触后致密区厚度、突触界面曲率降低（P＜0.05）.结论 脊髓mTOR信号通路可能通过调节脊髓背角突触结构可塑性参与大鼠神经病理性痛的形成.Objective To investigate the role of mammlian target of rapamycin （mTOR） signaling pathway in the spinal cord in the development of neuropathic pain （NP） in rats.Methods Twenty adult male SpragueDawley rats,weighing 180-220 g,were randomly divided into d groups （n =5 each） using a random number table：control group （group C）,sham operation group （group S）,NP group,and rapamycin group （group R）.Intrathecal catheters were successfully implanted in the rats except those in group C and observed for 3 days.In group S,the left sciatic nerve was only exposed but not ligated.NP was produced by clamping the left sciatic nerve.In group R,rapamycin 10 μl was injected intrathecally at 4 h after NP for 3 consecutive days.At 1 day before operation and 3,5 and 7 days after NP,the mechanical pain threshold （MPT） was measured and the changes in synaptic structure and organelles in the 1amine Ⅱ of the spinal dorsal horn were studied with transmission electron microscope and stereological analysis.Results Compared with C and S groups,MPT was significantly decreased,the numerical density of all synapses,spine synapses,negative synapses and perforated synapses,thickness of the postsynaptic density and curvature of the synaptic interface were increased at 5 and 7 days after ligation in NP and R groups （P 〈 0.05 or 0.01）.Compared with NP group,MPT was significantly increased,the numerical density of all synapses,spine synapses,negative synapses and perforated synapses,thickness of the postsynaptic density and curvature of the synaptic interface were decreased at 5 and 7 days after ligation in R group （P 〈 0.05）.Conclusion mTOR signaling pathway in the spinal cord is involved in the development of NP in rats possibility through regulating synaptic plasticity in the spinal dorsal horn.

关 键 词：脊髓 受体作用蛋白丝氨酸苏氨酸激酶类 神经痛 

分 类 号：R651[医药卫生—外科学]