小胶质细胞抑制剂对佐剂性关节炎大鼠脊髓促炎性细胞因子的影响

Effect of microglial inhibitor on spinal proinflammatory cytokines of adjuvant arthritic rats

目的:观察小胶质细胞抑制剂对佐剂性关节炎大鼠脊髓促炎性细胞因子的影响。方法:蛛网膜下腔置管成功的雄性SD大鼠分别脊髓蛛网膜下腔注射(it)生理盐水(NS)和米诺环素50μg,30 min后右踝关节皮内注射完全氟氏佐剂(CFA),it,qd,连续7 d,观察CFA后0,2,6,13 d后爪热刺激回缩潜伏期(PWTL)的变化及CFA致炎后0,2,6 d给药后4 h和13 d脊髓IL-1β,IL-6,TNF-α含量变化,这些促炎性细胞因子的表达水平通过ELISA方法检测。结果:米诺环素能抑制PTWL缩短;CFA致炎后脊髓IL-1β,IL-6,TNF-α表达明显增加,米诺环素可减少相应时间点脊髓IL-1β,IL-6,TNF-α的表达水平。结论:蛛网膜下腔注射米诺环素可以减少外周炎症诱导的脊髓促炎性细胞因子的分泌;脊髓小胶质细胞可能通过促炎性细胞因子介导炎性痛觉过敏。

Objective：To investigate the expression levels of spinal proinflammatory cytokines in adjuvant arthritis rats and the effect of intratheacl minocycline.Methods： After intrathecal catheter was implanted successfully between L3 and L4 vertebrae,adult male Sprague-Dawley（SD） rats were pretreated with normal saline or minocycline 50 μg for 30 min prior to intradermal injection of 50 μL complete freunds adjunvant（CFA） in the right ankle joint,intrathecal normal saline or minocycline was injected once daily for seven consecutive days.Paw withdrawal thermal latency（PWTL） was assessed on 0,2,6 and 13 days.The changes of spinal proinflammatory cytokines IL-1β,IL-6 and TNF-α levels were examined by ELISA analysis after 4 hours following intrathecal normal saline or minocycline at 0,2,6 d and 13 days after CFA injection.Results： Minocycline administered intratheaclly inhibited shortening of PWTL.The expression levels of IL-1β,IL-6 and TNF-α in the spine cord were obviously increased after CFA injection.It markedly inhibited the increase of spinal IL-1β,IL-6 and TNF-α levels at corresponding time point.Conclusion： Intratheacl minocycline could inhibit the increase of CFA-induced spinal proinflammatory cytokines.Spinal microglia perhaps mediates the inflammatory hyperalgesia by proinflammatory cytokines.