PKC抑制剂对甲醛诱导的内脏炎性痛大鼠脊髓ERK1/2磷酸化的影响  

EFFECT OF PKC INHIBITOR ON ERK1/2 PHOSPHORYLATION IN SPINAL CORD OF RATS WITH INFLAMMATORY VISCERAL PAIN INDUCED BY FORMALIN

作　　者：张家君[1] 岳伟[2] 张灿文 牛敬忠[3] 胡冬梅[3] 袁慧[3] 杨明峰[3] 张颜波[3] ZHANG Jia-Jun;YUE Wei;ZHANG Can-Wen;NIU Jing-Zhong;HU Dong-Mei;YUAN Hui;YANG Ming-Feng;ZHANG Yan-Bo(Department of Ultrasound Medicine,Affiliated Hospital of Taishan Medical University,Taian 271000,China;Department of Gastroenterology,Affiliated Hospital of Taishan Medical University,Taian 271000,China;Department of Neurology,Affiliated Hospital of Taishan Medical University,Taian 271000,China)

机构地区：[1]泰山医学院附属医院超声科,泰安271000 [2]泰山医学院附属医院消化科,泰安271000 [3]泰山医学院附属医院神经内科,泰安271000

出　　处：《中国疼痛医学杂志》2018年第4期249-253,共5页Chinese Journal of Pain Medicine

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);泰山医学院高层次培育课题(2016GCC02)

摘　　要：目的:探讨蛋白激酶C(protein kinase C,PKC)抑制剂H-7对福尔马林诱导的内脏炎症痛大鼠脊髓细胞外调节蛋白激酶1/2(extracellular regulated protein kinases,ERK1/2)磷酸化的影响。方法:清洁级雄性SD大鼠,重200~250 g,随机分为5组:正常对照组(N组);甲醛直肠致炎组(F组);甲醛直肠致炎和脊髓蛛网膜下腔内插管组(IT组);甲醛直肠致炎、脊髓蛛网膜下腔内插管并注射生理盐水组(NaCl组);甲醛直肠致炎、脊髓蛛网膜下腔内插管并注射H-7组(H-7组);每组大鼠24只,共120只。5组大鼠,每组8只,每15 min进行一次疼痛计分,连续记录大鼠的行为120 min;在甲醛造模后30 min、60 min和120 min取出L_6-S_1节段脊髓进行ERK1/2磷酸化检测。结果:F、IT、NaCl组和H-7组大鼠在注射甲醛后30 min均达到疼痛评分的最大值。H-7组在前90 min内疼痛分数显著低于F组(P<0.05或P<0.01)。与N相比,F组甲醛直肠黏膜注射后脊髓ERK1/2磷酸化水平增加,30 min时达最高水平,60 min时仍高于对照组,有显著性差异(P<0.05或P<0.01);与N相比,H-7组甲醛直肠黏膜注射后脊髓ERK1/2磷酸化水平也增加,30 min时达最高水平,60 min时仍高于对照组,有显著性差异(P<0.05或P<0.01);在甲醛注射后60 min内,H-7组与F组相比,ERK1/2磷酸化水平明显下降,有显著性差异(P<0.05或P<0.01)。结论:PKC抑制剂H-7能降低内脏炎症痛疼痛评分和抑制脊髓ERK1/2磷酸化水平,ERK1/2是PKC的下游信号通路在内脏炎症痛发病机制中起重要作用,对内脏炎症痛靶向治疗具有重要意义。Objective:To explore the effect of H-7,a PKC inhibitor,on the ERK1/2 phosphorylation in the spinal cord of rats with inflammatory visceral pain induced by formalin.Methods:One hundred and twenty male,SD rats(clean grade,weighing 200-250 g)were randomly divided into five groups(24 rats/group):normal control group(N);formalin-induced rectal inflammation group(F),formalin-induced rectal inflammation and spinal subarachnoid intubation group(IT),formalin-induced rectal inflammation and spinal subarachnoid intubation with the injection of normal saline(NaC1),formalin-induced rectal inflammation and spinal subarachnoid intubation group with the injection of H-7(H-7).The score of visceral inflammatory pain(SVIP)was recorded eight times respectively with 15 min intervals.ERK1/2 phosphorylation in the spinal cord was examined at 30,60 and 120 min following the treatment.Results:SVIP reached peak at the time point of 30 min after injection in group F,IT,NaCl and H-7.SVIP in group H-7 was significantly lower than that in group F in 0-90 min(P<0.05 or P<0.01).The level of ERK1/2 phosphorylation in group F and H-7 was increased after the injection,and reached peak 30 min after the injection,but it was still higher than that in group N 60 min after the injection(P<0.05 or P<0.01).The level of ERK1/2 phosphorylation in group H-7 was significantly lower than that in group F in 0-60 min(P<0.05 or P<0.01).Conclusion:H-7(an inhibitor of PKC)can decrease SVIP and inhibit ERK1/2 phosphorylation in the spinal cord.ERK1/2,as the downstream signaling pathways of PKC,perhaps plays an important role in the pathogenesis of inflammatory visceral pain.

关 键 词：蛋白激酶C(PKC) 脊髓细胞外调节蛋白激酶1/2(ERK1/2) 内脏 炎症痛 H-7 

分 类 号：R402[医药卫生—临床医学]