舒芬太尼对神经病理性疼痛大鼠脊髓趋化因子受体及p38丝裂原激活蛋白激酶的影响

Effect of sufentanil on chemokine receptors and p38 mitogen activated protein kinase in neuropathic pain rats

目的探讨舒芬太尼对神经病理性疼痛(neuropathic pain,NP)大鼠脊髓趋化因子受体及p38丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)的影响.方法采用随机数字表法将54只成年健康SD大鼠分为假手术组(S组)、坐骨神经慢性压迫性损伤(chronic constriction injury,CCI)模型组(CCI组)、舒芬太尼组(Suf组),每组18只.CCI组和Suf组采用CCI法制备大鼠NP模型.Suf组于术后每天腹腔注射舒芬太尼(10μg/kg),S组和CCI组则注射等容量的生理盐水.于术前1 d(T0)、术后3 d(T1)、术后7 d(T2)、术后14 d(T3)测定机械刺激缩足反射阈值(paw mechanical withdrawal threshold,PMWT)和热刺激缩足反射潜伏期(paw withdraw thermal latency,PWTL),采用Western blot法检测脊髓背角CC趋化因子受体2(C-C chemokine receptor type 2,CCR2)、CX3C趋化因子受体-1(C-X3-C motif chemokine receptor 1,CX3CR1)、总p38MAPK(total p38MAPK,t-p38)、磷酸化p38MAPK(phosphorylated p38MAPK,p-p38)及NF-κB p65蛋白表达水平.结果与S组比较,CCI组和Suf组T1~T3时PMWT和PWTL明显降低(P<0.05),脊髓背角CCR2、CX3CR1、p-p38及NF-κB p65蛋白水平明显增加(P<0.05);与CCI组比较,Suf组T1~T3时PMWT和PWTL明显升高,脊髓背角CCR2、CX3CR1、p-p38及NF-κB p65蛋白水平明显降低(P<0.05).结论舒芬太尼能降低趋化因子受体CCR2、CX3CR1的表达,抑制脊髓背角p38MAPK及NF-κB的活化,减轻NP大鼠的疼痛反应.

Objective To investigate the effect of sufentanil on chemokine receptors and p38 mitogen activated protein kinase(MAPK)in neuropathic pain(NP)rats.Methods Fifty-four adult Sprague Dawley(SD)rats were divided into the sham operation group(S group),chronic constriction injury(CCI)group(CCI group)and sufentanil group(Suf group)by random number table method,with 18 rats in each group.In CCI group and Suf group,NP rat models were made by CCI.Suf group received daily intraperitoneal injection of sufentanil(10μg/kg)after operation,while S group and CCI group received the same volume of physiological saline.Paw mechanical withdrawal threshold(PMWT)and paw withdraw thermal latency(PWTL)were measured at 1 d before operation(T0),3 d(T1),7 d(T2),and 14 d(T3)after operation.The expression of C-C chemokine receptor type 2(CCR2),C-X3-C motif chemokine receptor 1(CX3CR1),total p38MAPK(t-p38),phosphorylated p38MAPK(p-p38)and nuclear factor-κB(NF-κB)p65 protein in the dorsal horn of the spinal cord were detected by Western blot.Results Compared with S group,PMWT and PWTL were significantly decreased in CCI group and Suf group at T1-T3(P<0.05).The levels of CCR2,CX3CR1,p-p38 and NF-κB p65 protein were significantly increased(P<0.05).Compared with CCI group,PMWT and PWTL were significantly increased in Suf group at T1-T3(P<0.05),while the levels of CCR2,CX3CR1,p-p38 and NF-κB p65 protein were significantly decreased in Suf group(P<0.05).Conclusions Sufentanil can reduce the expression of chemokine receptors CCR2 and CX3CR1,inhibit the activation of spinal dorsal horn p38MAPK and NF-κB,and alleviate the pain response of NP rats.