脊髓TLR4/p38MAPK级联活化介导持续性术后痛时TNF-α的增加  

ACTIVATION OF TLR4-P38MAPK CASCADE MEDIATES THE ELEVATED LEVELS OF TNF-α IN SPINAL CORD IN A RAT MODEL OF PERSISTENT POSTOPERATIVE PAIN EVOKED BY SKIN/MUSCLE INCISION AND RETRACTION

作　　者：胡兴国[1] 阳红艳[2] 文锟 张云翔[1] 曾因明[3] 

机构地区：[1]湖南省桃源县人民医院麻醉科,桃源415700 [2]浙江大学邵逸夫医院麻醉科,杭州310016 [3]徐州医科大学江苏省麻醉学重点实验室&江苏省麻醉与镇痛应用技术重点实验室,江苏221002

出　　处：《中国疼痛医学杂志》2016年第1期23-27,共5页Chinese Journal of Pain Medicine

基　　金：湖南省高层次卫生人才225工程培养对象资助课题;湖南省科技计划一般项目资助课题(2009SK3018);江苏省教育厅高校省级重点实验室开放课题(KJS1106)

摘　　要：目的:研究脊髓肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)在持续性术后痛中的作用及与Toll样受体4(TLR4)/p38有丝分裂原活化蛋白激酶(p38MAPK)级联的关系。方法:选择鞘内置管成功的雄性SD大鼠120只,采用随机数字表法随机分为5组(每组24只):假手术组、持续性术后痛组、Toll样受体4小干扰RNA组(TLR4 si RNA组)、4-(4-氟苯基)-2-(4-甲磺酰基苯基)-5-(4-吡啶基)咪唑组(SB203580组)和重组人Ⅱ型肿瘤坏死因子组(rh TNFR-Fc组)。按Flatters介绍的方法建立大鼠皮肤肌肉切口牵拉(skin/muscle incision and retraction,SMIR)持续性术后痛模型;在术前1天及术后第1、3、7、12和22天时测定大鼠机械缩足反应阈值(mechanical withdrawal threshold,MWT);按ELISA法测定脊髓TNF-α含量。结果:与术前基础值及假手术组比较,持续性术后痛组大鼠在术后第3、7、12和22天MWT明显降低(P<0.05),脊髓TNF-α含量在术后7、12和22天明显升高(P<0.05);与持续性术后痛组比较,TLR4 si RNA组和SB203580组大鼠在术后第3、7和12天,rh TNFR-Fc组在术后第7和12天MWT明显升高(P<0.05),TLR4 si RNA组、SB203580组和rh TNFR-Fc组大鼠脊髓TNF-α含量在术后第7、12和22天明显降低(P<0.05)。结论:脊髓TNF-α参与了大鼠SMIR持续性术后痛的形成,其增加与脊髓TLR4/p38MAPK级联的活化有关。Objective： To study the role of tumor necrosis factor-oL （TNF-ot ） in the spinal cord in the development of persistent postoperative pain and the relationship between toll-like receptor 4 （TLR4）- p38 mitogen-activated protein kinases （p38MAPK） cascade. Methods： 120 male SD rats weighing 200-250g with intrathecal catheter （i.t） were randomly divided into five groups （~ = 24 each）： sham operation group, persistent postoperative pain group, toll-like receptor 4 small interference RNA group （TLR4 siRNA group）, 4-（4-Fluorophenyl）-2-（4-methylsulfonyl phenyl）- 5-（4-pyridyl）lH-imidazole group （SB203580 group） and tumor necrosis factor receptor-antibody recombination fusion protein group （rh TNFR-Fc group）. Persistent postoperative pain evoked by skin/muscle incision and retraction （SMIR） was established according to the method described previously. Pain behavior was assessed by mechanical withdrawal threshold （MWT） at 1 day before and 1, 3, 7, 12 and 22 days after operation. The content of TNF- a in spinal cord was assayed by enzyme-linked immunosorbent assay （ELISA）. Results： Compared with baseline of pre-operation and sham operation group, the MWT in persistent postoperative pain group decreased significantly at 3, 7, 12 and 22 days after operation （P 〈 0.05）, the content of TNF- α in the spinal cord in persistent postoperative pain group increased significantly at 7, 12 and 22 days after operation （P 〈 0.05）; Compared with persistent postoperative pain group, the MWT in TLR4 siRNA group and SB203580 group increased significantly at 3, 7 and 12 days after operation （P 〈 0.05）, the MWT in rh TNFR-Fc group increased significantly at 7, 12 days after operation （P 〈 0.05）, the content of TNF- α in the spinal cord in TLR4 siRNA group, SB203580 group and rh TNFR-Fc group decreased significantly at 7, 12 and 22 days after operation （P 〈 0.05）. Conclusion： TNF- a in the spinal cord is involved in the development of persistent post

关 键 词：肿瘤坏死因子Α TOLL样受体4 p38有丝分裂原活化蛋白激酶 术后痛 脊髓 

分 类 号：R614[医药卫生—麻醉学]