目的:探究肿瘤坏死因子α(tumor necrosis factorα,TNF-α)抑制剂XPro1595对大鼠脊神经结扎诱导的痛行为及脊髓背角白介素1β(IL-1β)、白介素6(IL-6)和TNF-α表达的影响。方法:运用L5脊神经结扎的方法建立神经病理性痛模型,通过鞘内注射给予TNF-α抑制剂(XPro1595)进行干预,采用Von Frey丝测定大鼠足底50%机械缩足反射阈值;运用Western Blot方法检测大鼠脊髓背角IL-1β、IL-6和TNF-α的表达情况。结果:(1)行为学结果显示:与对照组相比,脊神经结扎后大鼠表现出明显的机械性痛敏(P〈0.01),且可被鞘内注射XPro1595有效改善(P〈0.01);(2)Western Blot结果显示:与对照组相比,脊神经结扎组大鼠脊髓背角IL-1β、IL-6和TNF-α的表达显著升高,且可被鞘内注射XPro1595明显抑制(P〈0.01)。结论:鞘内注射XPro1595能够显著改善大鼠脊神经结扎诱导的神经病理性痛,其机制与抑制脊髓背角IL-1β、IL-6和TNF-α等炎性细胞因子的表达有关。
Objective: To explore the effectof XPro1595,a TNF-α inhibitor,on spinal nerve ligation( SNL)-induced nociceptive behavior and expressions of interleukin-1 beta( IL-1β),interleukin-6( IL-6),and tumor necrosis factor α( TNF-α) after SNL in the spinal dorsal horn. Methods: L5 spinal nerve ligation was used to build neuropathic pain model. XPro1595 was administered intrathecally( i. t.). Mechanical allodynia was tested with Von Frey filaments. Expression of inflammatory cytokines( IL-1β,IL-6 and TNF-α) were examined by Western Blot. Results:( 1) Behavioral tests showed that the mechanical threshold of SNL-rats had significantly decreased comparedwith the sham group( P〈0. 01),and the administration ofX Pro1595 can elevated mechanical allodynia apparently( P〈0. 01);( 2) Results of Western Blot indicated that expression of cytokines( IL-1β,IL-6 and TNF-α etc.) in SNL group were up-regulated compared with the sham( P〈0. 01),and these changes were inhibited by XPro1595apparently( P〈0. 05). Conclusion: Intrathecal injection of XPro1595 can effectively improve the mehcanical allodynia induced by neuropathic pain through down-regulation of cytokines,such as IL-1β,IL-6 and TNF-α,etc.