鞘内注射TRESK基因重组腺病毒对神经病理性痛大鼠脊髓p38MAPK和ERK活性的影响  

Effect of intrathecal TRESK gene recombinant adenovirus on activities of p38MAPK and ERK in spinal cord of rats with neuropathic pain

作　　者：周俊[1] 王汉兵[1] 仲吉英[1] 郑雪琴[1] 林森[1] 黄振兴[1] 黄腾[1] 杨承祥[1] 

机构地区：[1]佛山市第一人民医院麻醉科,528000

出　　处：《中华麻醉学杂志》2015年第4期470-473,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金（81300974）

摘　　要：目的 探讨鞘内注射TRESK基因重组腺病毒对神经病理性痛大鼠脊髓p38丝裂原活化蛋白激酶（p38MAPK）和细胞外信号调节蛋白激酶（ERK）活性的影响.方法 健康雄性SD大鼠36只,体重200～ 250 g,采用随机数字表法,将其分为6组（n=6）：空白对照组（C组）、假手术组（S组）、神经病理性痛组（NP组）、TRESK过表达腺病毒组（TRESK组）、阴性腺病毒组（Virus组）和生理盐水组（NS组）.采用坐骨神经分支选择性损伤法制备神经病理性痛模型.TRESK组、NS组和Virus组于造模成功后即刻分别鞘内注射pAd/CMV/V5-DEST-TRESK 25 μl（109 IU/ml）、阴性腺病毒25μl和生理盐水25μl.于造模前1d和造模后1、3、7 d（T0-3）时测定机械缩足反应阈（MWT）和热缩足潜伏期（TWL）.于造模后7d痛阈测定结束后,处死大鼠,取脊髓组织,采用Western blot法测定脊髓p38MAPK和ERK磷酸化水平.结果 与C组比较,NP组、TRESK组、Virus组和NS组T1～3时MWT降低,脊髓p38MAPK和ERK磷酸化水平升高（P＜0.05）.与NP组比较,TRESK组T1～3时MWT升高,脊髓p38MAPK和ERK磷酸化水平降低（P＜0.05）,Virus组和NS组差异无统计学意义（P＞0.05）.6组大鼠各时点TWL组间比较差异无统计学意义（P＞0.05）.结论 鞘内注射TRESK基因重组腺病毒减轻大鼠神经病理性痛的机制与可能与抑制脊髓p38MAPK和ERK的活性有关.Objective To evaluate the effects of intrathecal TRESK gene recombinant adenovirus on the expression of p38 mitogen-activated protein kinase （p38MAPK） and extracellular signal-regulated kinase （ERK） in the spinal cord of rats with neuropathic pain.Methods Thirty-six male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 6 groups （n=6 each） using a random number table：control group （group C）;sham operation group （group S）;neuropathic pain group （group NP）;TRESK overexpression adenovirus group （group TRESK）;negative adenovirus group （group Virus）;normal saline group （group NS）.The rats underwent spared nerve injury （SNI） to establish the nodel of neuropathic pain.In TRESK,NS and Virus groups,pAd/CMV/V5-DEST-TRESK 25 μl （109 IU/ml）,negative adenovirus 25 μl and normal saline 25 μl were intrathecally injected,respectively,immediately after SNI.At 1 day before SNI （baseline,T0） and 1,3 and 7 days after SNI （T1-3）,the mechanical paw withdrawal threshold （MWT） and thermal paw withdrawal latency （TWL） were measured.The rats were sacrificed after the last measurement of pain threshold at T3.The lumbar segments （L4,5） of the spinal cord were removed for determination of phosphorylation of p38MAPK and ERK by Western blot.Results Compared with group C,the MWT was significantly decreased at T1-3,and the phosphorylation of p38MAPK and ERK was increased in NP,TRESK,Virus and NS groups.Compared with group NP,the MWT was significantly increased at T1-3,and the phosphorylation of p38MAPK and ERK was decreased in group TRESK,and no significant change was found in phosphorylation of p38MAPK and ERK in Virus and NS groups.There was no significant difference in TWL between the six groups.Conclusion Inhibited activities of p38MAPK and ERK in the spinal cord may be involved in the mechanism by which intrathecal TRESK gene recombinant adenovirus alleviates neuropathic pain in rats.

关 键 词：钾通道 转染 注射 脊髓 P38丝裂原活化蛋白激酶类 细胞外信号调节MAP激酶类 神经痛 脊髓 

分 类 号：R965[医药卫生—药理学]