柳氮磺胺吡啶在神经病理性疼痛大鼠中的镇痛作用

Analgesic effect of sulfasalazine on neuropathic pain in rats

目的:研究柳氮磺胺吡啶(sulfasalazine,SFZ)对大鼠坐骨神经结扎(CCI)引起的神经病理性疼痛的镇痛作用,并探讨其对脊髓背角胶质细胞活化、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和白介素-6(IL-6)产生的影响。方法:将SD大鼠随机分为3组,即假手术(Sham)组、CCI组与SFZ组。建立大鼠CCI模型,按65 mg·kg-1灌胃(ig)给予SFZ,使用von Frey纤维丝测定大鼠机械缩足阈值(MWT)。应用免疫荧光染色法和Western blot法检测小胶质细胞标记物Iba-1及星型胶质细胞标记物GFAP的表达变化。采用RT-q PCR法检测TNF-α,IL-1β和IL-6的mRNA水平。结果:CCI组MWT值与Sham组相比显著降低(P<0.05);SFZ组MWT值较CCI组显著升高(P<0.05)。CCI组Iba-1和GFAP表达水平明显高于Sham组(P<0.05);SFZ组Iba-1表达水平与CCI组相比没有显著差异(P>0.05),SFZ组GFAP表达水平低于CCI组(P<0.05)。CCI组TNF-α,IL-1β和IL-6 mRNA水平与Sham组相比显著升高(P<0.05);SFZ组TNF-α,IL-1β和IL-6 mRNA水平较CCI组显著降低(P<0.05)。结论:SFZ可能通过抑制脊髓星型胶质细胞激活和炎症因子释放从而缓解CCI引起的神经病理性疼痛。

Objective： To explore the effect of sulfasalazine（ SFZ） on neuropathic pain caused by chronic constriction injury（ CCI） of sciatic nerve in rats,the expression of inflammatory cytokines（ TNF-α,IL-1β and IL-6） and activation of spinal glial cells in dorsal horn of spinal cord. Methods： SD rats were randomly divided into 3 groups（ Sham group,CCI group and SFZ group）. CCI was used to build neuropathic pain model. The rats were given 65 mg·kg-1 SFZ by intragastric administration（ ig）. Mechanical withdrawal threshold（ MWT） was measured by von Frey filaments. The expression levels of Iba-1 and GFAP in spinal cord of rats were detected by Western blotting and immunofluorescent staining. The effect of SFZ administration on mRNA expression of TNF-α,IL-1β and IL-6 was analyzed by real-time q PCR. Results： The MWT value of CCI group was significantly lower than that of Sham group（ P 〈 0. 05）; the MWT value of SFZ group was significantly higher than that of CCI group（ P 〈 0. 05）. The expression levels of Iba-1 and GFAP in CCI group was significantly higher than that in Sham group（ P 〈 0. 05）; the expression level of Iba-1 in SFZ group was not significantly different from that in CCI group（ P 〉 0. 05）; the expression of GFAP in SFZ group was lower than that in CCI group（ P 〈 0. 05）. The levels of TNF-α,IL-1β and IL-6 mRNA in CCI group were significantly higher than those in Sham group（ P 〈 0. 05）; the TNF-α,IL-1β and IL-6 mRNA levels in SFZ group were significantly lower than those in CCI group（ P 〈 0. 05）.Conclusion： SFZ may attenuate CCI-induced neuropathic pain by inhibiting the activation of spinal astrocytes andthe production of TNF-α,IL-1β,and IL-6.