M8046对神经病理性疼痛大鼠脊髓和背根节COX-2/PGE_2表达的影响

Effect of M8046 on expression of COX-2/PGE_2 in spinal cord and DRG in rats with neuropathic pain

目的:探讨糖皮质激素受体拮抗剂M8046对CCI大鼠脊髓和背根神经节环氧酶-2(COX-2)、前列腺素E2(PGE2)表达的影响及相关机制。方法:144只成年雄性SD大鼠,随机分为假手术组(Sham组)、模型对照组(CCI组)、M8046治疗组(M8046组)、溶剂对照组(SC组),每组36只,采用坐骨神经结扎制备神经病理性疼痛模型。Sham组仅暴露坐骨神经,不结扎。各组分别于术前1 d及术后1、3、7、10、14 d分别测定右后肢机械缩足反应阈值(PMWT)和热缩足反射潜伏期(PTWL);于术后3、7、14 d痛阈测定结束后取腰膨大脊髓及L4-5背根神经节,采用免疫组化和ELISA法测定COX-2、PGE2的表达。结果:与Sham组比较,CCI组术后各时间点PTWL、PMWT明显降低(P<0.05),且在术后第3天降至最低;与CCI组比较,M8046组术后第7、10、14天PMWT、PTWL明显增高(P<0.05)。同时,与Sham组相比,CCI大鼠脊髓组织的COX-2、PGE2表达明显增多(P<0.05),而与CCI组相比,M8046组明显减少COX-2阳性细胞及催化产物PGE2的表达(P<0.05),而背根神经节的表达结果与脊髓相似。结论:M8046对坐骨神经压迫性损伤大鼠的镇痛效应可能与抑制大鼠脊髓及背根神经节中COX-2、PGE2的表达有关。

Objective： To investigate the effects of glucocorticoid receptor antagonist-M8046 on the behavior and the cyclooxygenase-2/ prostaglandin E2（COX-2/PGE2） expression in spinal cord dorsal horn and dorsal root ganglia （DRG） in chronic constrictive injury （CCI） rats. Methods： One hundred and forty-four male SD rats were randomly divided into 4 groups, 36 rats in each group： Sham operation group （Sham）, chronic constrictive group （CCI）, M8046 treated group （M8046） and solvent controlled group （SC）. M8046 3 nag/（kg. d） in- traperitoneal injection was given after operation in group M8046. Paw thermal withdrawal （PTWL） and paw mechanical withdrawal threshold （PMWT） of rats were measured on 2 pre-operative and 1, 3, 7, 10, 14 pest-operative days. The spinal cord and Ln-s DRG of the operated side was removed at 3, 7, 14 days after surgery. The change of COX-2 and PGE2 expression was determined by immunohistochemical staining and EIJSA separately. Results： PTWL and PMWT in CCI group were significantly lower than those in Sham group on every post-operative day （P〈0.05）. FI＇WL and PMWT in M8046 group were significantly higher than those in CCI group on 7, 10, 14 pest-operative day （P 〈 0.05）. In spinal dorsal horn, the level of COX-2 and PGE2 expression in CCI group was significantly higher than that in Sham group （ P 〈 0.05）. M8046 could significantly attenuate the activation of COX-2 and PGE2 induced by CCI （ P 〈 0.05）. The expression of COX-2 and PGE2 in DRG was similar to that in spinal dorsal horn. Condusion： The effects of M8046 ameliorate the CCI-induced neuropathic pain may be related to attenuate the expression of COX-2 and PGE2 in spinal cord and DRG.