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观察鞘内注射姜黄素对坐骨神经慢性压迫性损伤(CCI)大鼠痛阈和脊髓组织Toll样受体4(TLR4)及TNF-α、IL-1β和IL-10表达的影响.鞘内置管的120只大鼠随机均分为4组:假手术组(Sham),CCI组,溶剂对照组(SC),姜黄素治疗组(Cur,100μg/天),建立CCI大鼠疼痛模型,术后第1、3、7、10和14天鞘内给药并测定痛阈,第3、7天取腰段脊髓第4～6节段(L4～L6)以Real-time PCR与Western blotting方法检测TLR4、HMGB1 mRNA和蛋白质的表达,ELISA法观察脊髓组织中TNF-α、IL-1β及IL-10表达变化.与Sham组相比,CCI组大鼠机械性痛阈与热痛阈显著降低(均P<0.05),同时脊髓组织TLR4、HMGB1 mRNA和蛋白质的表达明显增加(均P<0.05),TNF-α、IL-1β与IL-10的含量也明显升高(均P<0.05);鞘内注射姜黄素明显降低脊髓TLR4、高迁移率族蛋白1(HMGB1),TNF-α和IL-1β的表达,显著升高脊髓IL-10的表达,同时明显改善CCI大鼠疼痛行为(P<0.05).姜黄素减轻神经病理性疼痛可能与下调TLR4途径促炎症因子表达有关,抑制TLR4途径有望成为治疗神经病理性疼痛的新策略.
To observe the effects of intrathecal curcumin on the pain threshold and the expression of toll like receptor 4 (TLR4), TNF-α, IL-1β and IL-10 in rats with chronic constriction injury (CCI) 120 rats were randomly divided into 4 groups: sham operation group, CCI group, solvent control group and curcumin treatment group (Cur, 100μg / day) 1, 3, 7, 10 and 14 days intrathecally and the pain threshold were determined. On the 3rd and 7th days, the 4th to 6th segments of lumbar spinal cord (L4 ~ L6) were detected by Real-time PCR and Western blotting to detect TLR4 , HMGB1 mRNA and protein, and the changes of TNF-α, IL-1β and IL-10 expression in spinal cord were observed by ELISA.Compared with Sham group, the mechanical pain threshold and thermal pain threshold of CCI group were significantly decreased (P <0.05). At the same time, the expressions of TLR4, HMGB1 mRNA and protein in spinal cord tissue were significantly increased (all P <0.05), while the levels of TNF-α, IL-1β and IL- Curcumin significantly decreased the expression of TLR4, HMGB1, TNF-α and IL-1β in the spinal cord, significantly increased the expression of IL-10 in the spinal cord and significantly improved the pain behavior in CCI rats (P < 0.05). Curcumin attenuates neuropathology Pain may be related to down-regulation of proinflammatory cytokine expression in the TLR4 pathway, and inhibition of the TLR4 pathway is expected to be a new strategy for the treatment of neuropathic pain.