摘要：
Objective: To explore the effect of H-7, a PKC inhibitor, on the ERK1/2 phosphorylation in the spi-nal 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 in-creased 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.%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.
