摘要目的 评价NF-κB信号通路在鞘内注射血小板活化因子(PAF)诱发大鼠痛敏中的作用.方法 鞘内置管成功的雄性SD大鼠64只,体重200～250 g,随机分为6组:人工脑脊液(ACSF)对照组(AC组,n=16)鞘内注射ACSF 10μl;PAF诱发大鼠痛敏组(PAF组,n=16)鞘内注射PAF 10μg(溶于10μl ACSF);二甲基亚砜(DMSO)对照组(DC组,n=8)和低、中和高剂量SC-514组(S1-3组,n=8)分别于鞘内注射PAF前2 h腹腔注射0.1%DMSO溶液2 ml、SC-514(溶于2 ml 0.1%DMSO溶液)10、50、100 mg/kg.分别于鞘内给药前、给药后5、15、30、45和60 min时测定机械痛阈和热痛阈,随后每间隔30 min测定1次,连续4 h,ELISA法检测脊髓TNF-α和IL-lβ的表达.结果 鞘内注射PAF可诱发机械痛敏和热痛敏,上调大鼠脊髓TNF-α和IL-1β的表达;Iκβ激酶-β抑制剂SC-514可剂量依赖性地减轻PAF诱发的痛敏,抑制脊髓TNF-α和IL-1β的表达上调.结论 NF-κB信号通路参与了鞘内注射PAF诱发大鼠痛敏的过程.

abstractsObjective To investigate the role of NF-κB pathway in the development of intrathecal(IT)platelet-activating factor (PAF)-induced hyperalgesia in rats. Methods Sixty-four male SD rats (200-250 g) in which intrathecal catheters were successfully implanted without complications were randomly divided into 6 groups:group Ⅰ received artificial cerebro-spinal fluid (ACSF) 10 μl IT (n = 16); group Ⅱ received PAF 10 μg in ACSF 10 μl IT; group Ⅲ received 0.1% DMSO 2 ml intraperitoneally (IP) (n = 8); group Ⅳ, Ⅴ, Ⅵ received IP SC-514 (a selective IKK-β inhibitor) 10, 50, 100 mg/kg in 0.1% DMSO 2 ml respectively at 2 h before IT PAF. Paw withdrawal threshold to mechanical stimulation (PWMT) and paw withdrawal latency to thermal stimuli (PWTL) were measured before (baseline) and at 5, 15, 30, 45, 60 min and then every 30 min for another 4 h after IT administration. The animals were killed after the last pain threshold measurement at 5 h after IT PAF. The lumbar segment (L4-6) of the spinal cord was removed for determination of TNF-α and IL-lβ content (by ELISA).Results lntrathecal PAF induced tactile allodynia and thermal hyperalgesia rapidly, increased the expression of TNF-α and IL-lβ in lumbar spinal cord. Pretreatment with SC-514 attenuated PAF-induced hyperalgesia and inhibited the increase in TNF-α and IL-1β expression in the spinal cord. Conclusion NF-κB is involved in intrathecal PAF-induced hyperalgesia.