鞘内注射SB203580对神经病理性疼痛大鼠脊髓背角环氧化酶-2表达的影响

摘要

目的：探讨鞘内注射p38丝裂原蛋白激酶(p38MAPK)特异性抑制剂SB203580对大鼠慢性压迫性损伤(CCI)术后脊髓背角环氧化酶-2(COX-2)蛋白表达的影响。方法：鞘内置管成功的SD雄性大鼠24只，随机分为4组：Sham组、NS组、DMSO组和SB组，其中Sham组做假手术，后3组大鼠右侧坐骨神经建立CCI模型。模型成功后，术后第6天开始分别鞘内注射生理盐水、2%二甲亚砜、SB203580，每天2次，连续5 d。术前1 d、术后第1，3，5，7，9，11天测定机械性痛阈。术后第11天测定机械性痛阈后处死大鼠，取脊髓腰膨大进行免疫组织化学分析测定COX-2蛋白表达。结果：与术前相比，Sham组术后机械性痛阈无明显改变(P>0.05)，NS组和DMSO组在术后第1至11天机械性痛阈降低(P<0.05)，SB组在术后第1至5天机械性痛阈降低(P<0.05)，与NS组和DMSO组比较，SB组在术后第7至11天，机械性痛阈增加(P<0.05)；免疫组织化学分析，NS组和DMSO组脊髓背角COX-2蛋白阳性细胞数和阳性评分均高于Sham组(P<0.05)，SB组COX-2蛋白阳性细胞数和阳性评分低于NS组和DMSO组(P<0.05)。结论：鞘内注射SB203580可使神经病理性疼痛大鼠产生明显镇痛效应；可减少神经病理性疼痛大鼠脊髓背角COX-2蛋白的表达，p38MAPK参与COX-2蛋白表达的调节。%Objective:To investigate the changes of cyclooxygenase-2 (COX-2) expression in the spinal cord dorsal horn atfer intrathecal a speciifc p38MAPK inhibitor-SB203580 on neuropathic pain in rats induced by chronic constrictive injury (CCI) to the sciatic nerve. Methods:Twenty-four male SD rats atfer intrathecal catheter placement were randomly divided into 4 groups:a sham group with sham surgery, the neuropathic pain model of a NS group, a DMSO group and an SB group were established by CCI to sciatic nerve. NS or DMSO or SB203580 was injected IT NS or 2%DMSO or SB203580 twice a day for 5 consecutive days starting at 6th day when the model of chronic constrictive injury was established. Mechanical stimuli were measured before the surgery and on 1st, 3rd, 5th, 7th, 9th, and 11th day atfer the surgery. hTen all rats were sacriifced and the lumbar segment of spinal cord was removed to determine the COX-2 expression in the dorsal horn by immunocytochemistry. Results:Day 1 to 11 after the surgery, the threshold to mechanical on the surgery side was signiifcantly lower in the NS group and the DMSO group than in the sham group. Day 7 to 11 atfer the sugery, the threshold to mechanical on the surgery side was signiifcantly lower in the SB group than in the NS group and the DMSO group. hTe expression of spinal COX-2 was higher in the NS group and the DMSO group than in the sham group, but lower in the SB group than in NS group and the DMSO group. Conclusion:Intrathecal administration of SB203580 has signiifcant analgesic effect in the CCI rat model. Expression of COX-2 is signiifcantly reduced when p38MAPK is inhibited by intrathecal SB203580, and p38MAPK stimulation is essential for COX-2 expression.