急性内脏炎症痛大鼠脊髓JNK磷酸化的改变及抑制剂镇痛的实验研究  

Changes of JNK phosphorylation in formalin-induced visceral inflammatory pain and effect of inhibitor in rats

作　　者：李美艺 耿彪 乔福珍 牛敬忠 张颜波 Li Meiyi;Geng Biao;Qiao Fuzhen;Niu Jingzhong;Zhang Yanbo(The Second Department of Neurology,Taishan Hospital of Shandong Province,Taian City,Shandong Province 271000,China;Department of Pharmacy,The Second Affiliated Hospital of Shandong First Medical University,Taian City,Shandong Province 271000,China;Department of Neurology,The Second Affiliated Hospital of Shandong First Medical University,Taian City,Shandong Province 271000,China)

机构地区：[1]山东省泰山医院神经内二科,泰安市271000 [2]山东第一医科大学第二附属医院药剂科,泰安市271000 [3]山东第一医科大学第二附属医院神经内科,泰安市271000

出　　处：《中华疼痛学杂志》2023年第4期587-593,共7页Chinese Journal Of Painology

基　　金：山东省自然科学基金(联合专项ZR2015HL041);山东省医药卫生科技发展计划(2014WS0506);教育部重大支撑计划(国家科技支撑计划2013BAI07B01);泰山医学院高层次课题培育计划(2016GCC02)。

摘　　要：目的探究内脏炎症痛过程中脊髓JNK磷酸化水平变化及JNK选择性抑制剂对炎症痛觉敏感化的作用。方法采用福尔马林直肠黏膜下注射诱导的内脏炎症痛模型,共170只雄性SD大鼠,按照随机数字表法随机分为5组,每组34例。对照组(N组)、福尔马林致炎组(F组)、福尔马林致炎和脊髓蛛网膜下腔内插管组(IT组)、IT+DMSO组(DMSO组)、IT+SP600125组(SP600125组),其中50只大鼠(每组10只)诱导模型后每隔15 min,共记录8个时点内脏炎症痛疼痛表现,通过痛觉评分公式计算出疼痛分数分析疼痛行为反应。另120只雄性SD大鼠(5组,每组每时段6只)诱导模型后30、60、90、120 min分别应用蛋白印迹法、Gel-DOC凝胶成像系统,分析大鼠L_(6)~S_(2)节段脊髓组织蛋白中JNK、p-JNK变化水平。通过比较疼痛评分、脊髓节段JNK、p-JNK变化分析炎症痛分子机制及抑制剂镇痛作用。结果造模30 min后各组疼痛评分达峰值,抑制剂组(60.03±3.04)较F组(85.96±4.40)、IT组(83.10±2.74)及DMSO组(86.67±3.32)能降低炎症痛模型大鼠疼痛评分,差异具有统计学意义(P均<0.05)。各实验组大鼠中JNK水平差异无统计学意义(P>0.05);与N组相比,F组致炎后30 min(8.90±0.51比4.49±0.28,t=31.38,P<0.001)、60 min(7.20±0.37比4.43±0.33,t=24.65,P<0.001)、90 min(6.50±0.33比4.53±0.21,t=17.34,P<0.001)时大鼠脊髓中JNK磷酸化水平较对照组显著升高(P均<0.05);SP600125组较F组、IT组、IT+DMSO组可明显抑制造模后30~90 min脊髓中JNK磷酸化水平,差异具有统计学意义(P均<0.05)。结论福尔马林致炎能升高大鼠脊髓JNK磷酸化水平,JNK选择性抑制剂SP600125可显著降低脊髓JNK磷酸化水平,抑制内脏炎症痛痛觉敏感化。Objective To observe the level of JNK phosphorylation and the effect of JNK inhibitor(SP600125)on acute inflammatory pain induced by formalin in rats.Methods One hundred and seventy male SD rats were randomly divided into 5 groups,34 rats in each group:controlled group(group N),formalin-induced rectal inflammation group(group F),formalin-induced rectal inflammation and spinal subarachnoid intubation group(group IT),formalin-induced rectal inflammation and spinal subarachnoid injection of DMSO group(group DMSO),formalin-induced rectal inflammation and spinal subarachnoid injection of SP600125 group(group SP600125).The score of visceral inflammatory pain(SVIP)were recorded every 15 min.The expression of JNK and p-JNK in spinal cord were tested by Western-blot and Gel-DOC imaging system.Results The level of SVIP reached their peak at 30 min after formalin injection,the SVIP was significantly lower in the group SP600125(60.03±3.04)than that in the group F(85.96±4.40),group IT(83.10±2.74)and group DMSO(86.67±3.32).The relative gray value of p-JNK was higher in the group F than that in the group N after formalin injection 30 min(8.90±0.51 vs.4.49±0.28,t=31.38,P<0.001),60 min(7.20±0.37 vs.4.43±0.33,t=24.65,P<0.001),90 min(6.50±0.33 vs.4.53±0.21,t=17.34,P<0.001).The level of p-JNK in the spinal cord was significantly inhibited 30-90 min after modeling,compared with other groups(all P<0.05).Conclusion JNK phosphorylation rises by inflammation reaction induced with formalin injection,and the selective JNK inhibitor SP600125 could reduce the SVIP and phosphorylation level of p-JNK in male rats.

关 键 词：JNK抑制剂 内脏炎症痛 脊髓 JNK JNK磷酸化 

分 类 号：R-332[医药卫生] R651.2