背根神经节NF-κB/p65激活介导的CX3CL1上调在大鼠膝关节骨性关节炎痛觉过敏中的作用

关键词：膝关节骨性关节炎  背根神经节  NF-κB/p65  CX3CL1  机械痛敏

Keywords:knee osteoarthritis  dorsal root ganglion  NF-κB/p65  CX3CL1  mechanical allodynia

摘要：

      摘要 目的：研究背根神经节中核转录因子-kappa B/p65（nuclear factor-kappa B/p65， NF-κB/p65）激活促进趋化因子CX3CL1（fractalkine）上调在膝关节骨性关节炎（knee osteoarthritis， KOA）诱导的痛觉过敏中的作用。 方法：采用体重为（220—250）g的成年雄性SD大鼠，随机地分为生理盐水对照组、KOA模型组、鞘内注射CX3CL1中和性抗体的KOA模型组和鞘内注射NF-κB活化抑制剂吡咯烷二硫代氨基甲酸酯（pyrrolidine dithiocarbamate， PDTC）的KOA模型组（n=12/组）。于造模前1天和造模后7、14、21、28天，采用Von Fray Hair检测大鼠术侧后爪的机械撤足阈值，采用Western Blot的方法检测各组大鼠背根神经节内的CX3CL1和磷酸化NF-κB/p65（p-p65）的表达情况。 结果：KOA模型组大鼠背根神经节内CX3CL1和p-p65的表达量较对照组明显增加，且表达增加趋势与机械痛阈的变化趋势相一致；与KOA模型组相比，鞘内注射CX3CL1中和性抗体缓解KOA引起的机械痛敏；此外，与模型组相比，在大鼠鞘内注射PDTC能够阻断KOA诱导的背根神经节CX3CL1表达上调，并缓解KOA引起的机械痛敏。 结论：背根神经节NF-κB/p65激活介导CX3CL1表达增加参与了KOA诱导的痛觉过敏。抑制背根神经节内NF-κB/p65的激活阻断KOA引起的CX3CL1的上调，从而缓解OA大鼠的痛觉过敏。

Abstract:

      Abstract Objective： To investigate the role of activated NF-κB/p65 (nuclear factor-kappa B/p65) mediated CX3CL1 (Fractalkine) upregulation in the development of KOA (Knee osteoarthritis)-induced allodynia. Method： Male SD rats (220—250)g were randomly divided into four groups： normal saline group， KOA group， KOA+anti-CX3CL1 antibody group and KOA+PDTC (pyrrolidine dithiocarbamate) group (n=12/group). The mechanical withdrawal thresholds were assessed by Von Fray Hair one day prior to surgery and 7， 14， 21， 28 days after operation. The expression of CX3CL1 and phosphorylated NF-κB/p65 (p-p65) in the dorsal root ganglion was detected by Western Blot at each time point. Result： Compared with the control group， the expression of CX3CL1 and p-p65 in the KOA model of rats were increased， which were consistent with the decreased mechanical withdrawal threshold in the KOA group. Intrathecal injection of anti-CX3CL1 antibody alleviated mechanical allodynia of KOA rats. In addition， intrathecal injection of PDTC inhibited the upregulation of CX3CL1 in dorsal root ganglion of KOA rats and alleviated mechanical allodynia of KOA rats. Conclusion： Upregulation of CX3CL1 expression mediated by activation of NF-kappa B/p65 in dorsal root ganglion contributes to KOA-induced mechanical allodynia in rats. Inhibition of NF-kappa B/p65 activation in dorsal root ganglion significantly prevents the up-regulation of CX3CL1 induced by KOA， thus alleviates the mechanical allodynia in KOA rats.