【摘要】 目的:观察鞘内注射PKC抑制剂对神经病理痛大鼠脊髓背角N-甲基-D-天冬氨受体(NMDAR)、降钙素基因相关肽(CGRP)表达的影响。方法:健康雄性SD大鼠36只,体重220~280g。随机分为4组(n=9):对照组(C组)、假手术组(Sham组)、坐骨神经分支选择结扎切断模型组(SNI组)和PKC抑制剂组(P组)。SNI组和P组制备SNI模型,P组在SNI术后14d内每天鞘内注射PKC抑制剂11μg,其余各组给予等容量生理盐水。在SNI术前1d(基础值)及术后14d每次注射药物后测定机械痛阈和热缩足潜伏期,分别于SNI术后2、7、14d注射药物后各处死大鼠3只,采用免疫组化法测定L5节段脊髓背角NMDAR和CGRP表达水平。结果:与C组和Sham组比较,SNI组机械痛阈降低,NMDAR和CGRP表达上调(P<0.01),热缩足潜伏期差异无统计学意义(P>0.05)。与SNI组比较,P组机械痛阈升提高,热缩足潜伏期延长,NMDAR和CGRP表达下调(P<0.01)。结论:鞘内注射PKC抑制剂对神经病理痛大鼠具有明显的抗伤害效应,并抑制大鼠脊髓背角NMDAR和CGRP表达。更多还原

【Abstract】 Objective:To investigate the effect of intrathecal protein kinase C inhibitor on N-methyl-D-aspartate receptors(NMDAR) and calcitonin gene-related peptide(CGRP) in the spinal dorsal horn in rats with neuropathic pain.Methods: 36 healthy male Sprague-Dawley rats(220~280g) were randomly divided into four groups(n=9): control group(group C),sham group(group Sham),spared sciatic nerve injury group(group SNI) and protein kinase C inhibitor group(group P).Both group SNI and group P were received a lesion to two of the three terminal branches of the sciatic nerve(tibial and common peroneal nerves) leaving the remaining sural nerve intact(spared nerve injury model,SNI).The rats in group P were intrathecally injected 11 μg protein kinase C inhibitor(Chelerythrine Chloride 11 μg) followed by 10μl normal saline once a day during 14 days post-surgery,respectively.Rats in group C,group Sham and group SNI were intrathecally injected 20μl normal saline in uniform interval.Mechanical pain threshold and thermal withdrawal latency were measured on day 1 pre-surgery(baseline) and every day during 14 days post-surgery after intrathecally injection.On day 2,7,14 post-surgery the rats were killed in batch(3 rats/batch) after intrathecal injection,and the expression of NMDAR and CGRP in the spinal dorsal horn of L5 segment were determined using immunohistochemistry.Results: Compared with group C and group Sham,mechanical pain threshold in group SNI was decreased,and the expression of NMDAR and CGRP immunoreactive soma in the superficial laminae of the L5 spinal dorsal horn was significantly increased(P<0.01),with no significant difference in thermal withdrawal latency(P>0.05).Compared with group SNI,mechanical pain threshold was elevated and thermal withdrawal latency was prolonged in group P and the expression of NMDAR and CGRP immunoreactive soma in the superficial laminae of the L5 spinal dorsal horn was decreased(P<0.01).Conclusions: Intrathecal administration of protein kinase C inhibitor can provide significant antinociception effect in rats with neuropathic pain,and the inhibition of NMDAR and CGRP is involved in the antinociception mechanism.更多还原