自噬在大鼠神经病理性痛形成中的作用  

Role of autophagy in development of neuropathic pain in rats

作　　者：冯涛[1,2] 翁泽林[1] 张建成[1] 袁世荧[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院麻醉与危重病医学教研室,武汉市430022 [2]湖北医药学院附属东风医院麻醉科

出　　处：《中华麻醉学杂志》2013年第11期1362-1364,共3页Chinese Journal of Anesthesiology

摘　　要：目的评价自噬在大鼠神经病理性痛形成中的作用。方法雄性sD大鼠30只，体重200～220g，采用随机数字表法分为3组（n=10）：假手术组（sham组）、神经病理性痛组（NP组）和自噬诱导剂雷帕霉素组（Rap组）。行L4,5鞘内置管后，NP组和Rap组行左侧L5脊神经结扎术制备大鼠神／经病理性痛模型，sham组大鼠仅暴露左侧L5神经但不结扎。Rap组大鼠分别于结扎前30min和术后2d鞘内注射雷帕霉素60μg，sham组和NP组注射等容溶剂（5％DMSO）。于结扎后1、3、5和7d（T1-4）时测定机械痛阈和热痛阈，T4时测完痛阈后处死大鼠取左侧L5节段脊髓背角，电镜下观察自噬体，采用Westernblot法检测微管相关轻链蛋白3Ⅱ（LC3Ⅱ）和泛素结合蛋白p62表达，ELISA法检测IL-1β含量。结果与sham组比较，NP组大鼠各时点机械痛阈和T2-4时热痛阈降低，T4时脊髓背角LC3Ⅱ、p62表达水平及IL-1β含量升高（P〈0．05）；与NP组比较，Rap组大鼠各时点机械痛阈和T2。时热痛阈及L时脊髓背角LC3Ⅱ表达水平升高，T4时脊髓背角p62表达水平及IL-1β含量降低（P〈0．05）。电镜下NP组和Rap组大鼠脊髓背角可见自噬体，Rap组细胞器受损程度较NP组轻。结论大鼠神经病理性痛的形成与自噬障碍有关。Objective To evaluate the role of autophagy in the development of neuropathic pain （NP） in rats. Methods Thirty male Sprague-Dawley rats, weighing 200-220 g, were randomly divided into 3 groups （ n = 10 each） using a random number table： sham operation group （sham group）, NP group and rapamycin （autophagy inducer） group （Rap group） . Intrathecal catheter was inserted into the subaraehnoid space and advanced caudally until the tip reached L4,5 segment. NP was induced by ligation of the left L5 spinal nerve （SNL） in NP and Rap groups. The L5 spinal nerve was only exposed, but not ligated in group sham. At 30 min before ligation and 2 days after operation, rapamyein 60 μg was injected intrathecally via the intratheeal catheter in Rap group, while the equal volume of vehicle （5 % dimethyl sulfoxide） was injected in sham and NP groups. The mechanical and ther- mal pain thresholds were measured on 1, 3, 5 and 7 days after ligation （T1-4） .The rats were sacrificed after the last measurement of pain threshold at T4 . The ipsilateral L5 segment of spinal dorsal horn was removed for examina- tion of autophagosomes （using transmission electron microscope） and for determination of the expression of LC3 Ⅱ and p62 （by Western blot） and content of IL-1β （by ELISA）. Results Compared with sham group, the mechani- cal pain threshold at each time point and thermal pain threshold at T2-4 were significantly decreased, and the LC3 Ⅱ and p62 expression and IL-1β content were increased at T4 in group NP （P 〈 0.05）. Compared with NP group, the mechanical pain threshold at each time point, thermal pain threshold at T2-4 and LC3 Ⅱ expression at 3？4 were significantly increased, and the p62 expression and IL-1β content were decreased at T4 in group Rap （ P 〈 0.05）.Microscopic examination showed that autophagosomes were observed in the spinal dorsal horn in NP and Rap groups, and the damage to organelles was lighter in Rap group than in NP group. Conclusion The development

关 键 词：自噬 神经痛 

分 类 号：R363[医药卫生—病理学]