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目的:探究肿瘤坏死因子α(tumor necrosis factorα,TNF-α)抑制剂XPro~1595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(XPro~1595)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XPro~1595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XPro~1595明显抑制(P<0.01)。结论:鞘内注射XPro~1595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 investigate the pain behavior induced by ligation of XPro ~ 1595, a tumor necrosis factorα (TNF-α) inhibitor, and the effects of interleukin-1β (IL-1β), interleukin- And TNF-α expression. Methods: The neuropathic pain model was established by ligation of L5 spinal nerve. The TNF-α inhibitor (XPro ~ 1595) was administered by intrathecal injection and the 50% mechanical reflex threshold was measured by Von Frey’s method. Western Blot method was used to detect the expression of IL-1β, IL-6 and TNF-α in spinal dorsal horn of rats. Results: (1) The behavioral results showed that compared with the control group, the rats showed obvious mechanical hyperalgesia (P <0.01) after ligation of the spinal nerves, and could be effectively improved by the intrathecal injection of XPro ~ 1595 (P < 0.01). (2) The results of Western Blot showed that compared with the control group, the expression of IL-1β, IL-6 and TNF-α in spinal dorsal horn of spinal cord ligation group was significantly increased, 1595 significantly inhibited (P <0.01). Conclusion: Intrathecal injection of XPro ~ 1595 can significantly improve the neuropathic pain induced by ligation of spinal nerves in rats, and its mechanism is related to the inhibition of the expression of IL-1β, IL-6 and TNF-α and other inflammatory cytokines in spinal dorsal horn.