| 摘要: |
| 目的:观察大鼠坐骨神经结扎(CCI)后脊髓背角Toll样受体4(TLR4)及脊髓内IL-1β、TNF-α表达的变化,探讨神经病理性疼痛可能的治疗靶点。方法:结扎大鼠右侧坐骨神经,术后1、3、7、10、14 d观察大鼠热痛阈及机械性痛阈的变化,采用实时定量RT-PCR、免疫荧光及Western印迹观察L4~L6 段脊髓组织TLR4基因及蛋白表达的变化,ELISA法测量脊髓组织IL-1β、TNF-α表达的变化；以假手组大鼠作为对照。结果:坐骨神经结扎后,大鼠右足热痛阈及机械性痛阈明显降低,脊髓背角TLR4基因及蛋白表达明显增加,明显高于假手术组(P<0.05)；脊髓组织IL-1β、TNF-α的含量也明显升高,明显高于假手术组(P<0.05)。结论:坐骨神经结扎可能通过诱导TLR4表达,促进下游细胞因子释放,导致痛阈降低；TLR4有望成为治疗病理性疼痛的新靶点。 |
| 关键词: Toll样受体4 神经病理性疼痛 坐骨神经结扎 白细胞介素1β 肿瘤坏死因子α |
| DOI：10.3724/SP.J.1008.2008.00949 |
| 投稿时间：2007-12-04修订日期：2008-02-14 |
| 基金项目: |
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| Changes of Toll-like receptor 4 and its downstream cytokines in spinal cord of rat model of neuropathic pain |
| SUN Yu-ming△,WU Fei-xiang△,MIAO Xue-rong,L Xin,XU Xue-wu,YANG Li-qun,WU Jing-xiang, YU Wei-feng* |
| (Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China) |
| Abstract: |
| Objective:To investigate the changes of toll-like receptor 4 expression and its downstream cytokines TNF-α, IL-1β in the spinal cord in rat chronic constriction injury (CCI) models, and to discuss the potential target for treatment of neuropathic pain.Methods: Neuropathic pain was produced by CCI of right sciatic nerve as described previously．On the 1st , 3rd, 7th and 14th day after surgery, the expression of TLR4 mRNA and protein in L4-L6 was assessed by RT-PCR and Western blotting, respectively; the distribution of TLR4 in the spinal cord was detected by immunofluorescence.The levels of TNF-α, IL-1β in the spinal cord were detected by ELISA.Thermal and mechanical nociceptive thresholds were assessed with paw withdrawal latency to radiant heat and von Frey filaments.Rats receive sham operation served as controls.Results: The mechanical allodynia and thermal hyperalgesia were induced in animals after CCI.The paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) of right paw were decreased after CCI (P<0.05), and the expression of TLR4 mRNA and protein was significantly increased (P<0.05); the levels of TNF-α and IL-1β in SF were also significantly increased after CCI compared with that in the sham control (P<0.05).Conclusion: CCI-induced toll-like receptor 4 activation may increase the expression of cytokines and subsequently decrease pain threshold, indicating that TLR4 might be a potential target for the treatment of neuropathic pain. |
| Key words: Toll-like receptor 4 neuropathic pain chronic constriction injury interleukin-1β tumor necrosis factor-α |
