【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200²50 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L₆-S₁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。更多还原

【Abstract】 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(NaCl), 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, Na Cl 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.更多还原