鞘内西地那非能减轻神经病理性疼痛大鼠的痛觉高敏

摘要

目的 观察鞘内注射西地那非对腰5(L5)脊神经切断大鼠痛觉高敏及对脊髓小胶质细胞活化、炎症细胞因子表达的影响.方法 ♂SD大鼠120只,随机分为5组(n=24),Ⅰ组:假手术组;Ⅱ组:L5脊神经切断模型鞘内注射生理盐水20 μl;Ⅲ～Ⅴ组:L5脊神经切断模型分别鞘内注射3 μg/20 μl、10 μg/20 μl、30 μg/20 μl西地那非组.Ⅰ组仅暴露L5脊神经,Ⅱ～Ⅴ组均切断L5脊神经,术后d7开始鞘内给药,Ⅰ、Ⅱ组注射20 μl生理盐水,Ⅲ～Ⅴ组分别给予上述剂量西地那非,各组每天1次,连续5 d.测定各组大鼠术前1 d,术后7、8、10、12 d机械痛阈(mechanical withdrawa1 threshold,MWT),术后8、10、12 d取L5脊髓,测定各组大鼠肿瘤坏死因子(tumor necrosis factor α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)含量和小胶质细胞标记物白细胞分化抗原11b(cluster differentiation antigen 11b,CD11b)的mRNA表达水平.结果 ①术后7 d,与Ⅰ组相比,各组MWT明显下降(P<0.05),术后8、10、12 d与Ⅱ组相比,Ⅲ～Ⅴ剂量依赖地升高MWT(P<0.05).②与Ⅰ组相比较,其余各组大鼠术后8、10、12 d TNF-α和IL-1β的水平及CD11b mRNA含量均明显上升(P<0.05),与Ⅱ组相比较,Ⅲ～Ⅴ于术后8、10、12 d明显剂量依赖地抑制了TNF-α和 IL-1β及CD11b mRNA的表达(P<0.05).结论 西地那非能剂量依赖性地缓解大鼠神经病理性痛觉过敏的发展,该效应可能与抑制脊髓小胶质细胞活性,减少TNF-α和 IL-1β表达有关.%Aim To observe the effect of intrathecal sildenafil on the hyperalgesia , the activity of spinal mi-croglia and the expression of proinflammatory cytokines in rats with L5 spinal nerve transected. Methods One hundred and twenty male SD rats were randomly divid -ed into 5 groups; group I in which sham operation was taken, group II to V in which L5 spinal nerve was transected. On post-surgical day 7, saline (20 μl) was administered intrathecally in groups I and II , while sildenafil was injected as 3 μg/20 μl,10 μg/20 μl,30 μg/20 μl in group III, IV and V respectively. The injection was given once a day and lasted for five days. Mechanical withdrawl threshold was determined in rats 1 day before operation, and on post-surgical days 7,8 , 10 and 12. On days 8,10 and 12 after operation, the rats were euthanized and the L5 segment of the spinal cord was collected to analyse the level of proinflammatory cytokines, such as TNF-α and IL-1β, as well as the expression of Mrna of CD lib-the specific marker for microglia. Results ① After L5 spinal nerve transec-tion, the MWT was significantly lower in groups II III, IV and V compared with that in group I on day 7; after intrathecal injection of sildenafil, the MWT in groups III, IV and V was markedly elevated in a dose dependent manner compared with group II on days 8, 10 and 12. ② On day 8,10 and 12 ,the levels of TNF-α,IL-1β and the Mrna level of CD 11b, in the spinal cord of the L5 segment were significantly elevated in groups II III, IV and V compared with those in group I ; after intrathecal injection of sildenafil , the expressions of TNF-α,IL-1β and Mrna of CD11b in groups IH, IV and V were markedly inhibited in a dose de -pendent manner compared with group II. Conclusions Intrathecal sildenafil can dose-dependently attenuate the hyperalgesia in rats with L5 spinal nerve transected , which might result from the suppression of the mi - crogial activity and the reduction in the levels of TNF -α and IL-1β.