摘要
目的：观察预防性腹腔给予己酮可可碱对大鼠腰5脊神经切断后机械痛觉过敏的作用，以及相应脊髓节段胶质细胞活化、炎症及细胞因子表达的影响。方法：雄性SD大鼠48只，随机均分为6组，每组8只。Ⅰ组为假手术组；Ⅱ组为等渗盐水对照组；Ⅲ组为12．5mg／kg己酮可可碱治疗组；Ⅳ组为25mg／kg己酮可可碱治疗组；Ⅴ组为50mg／kg己酮可可碱治疗组；Ⅵ组为100mg／kg己酮可可碱治疗组。采用大鼠腰5脊神经切断神经病理性疼痛模型，术前1h，Ⅰ和Ⅱ组腹腔注射等渗盐水，Ⅲ-Ⅵ组腹腔注射相应剂量的己酮可可碱。术后第1—6d每天16时，各组大鼠腹腔注射相应剂量药物。计数手术前、术后第1、4、7d各组大鼠2g和12g范氟雷丝刺激手术同侧后爪后跟撤腿次数。术后第7d行为学检测完毕，处死大鼠，取腰5脊髓，测定肿瘤坏死因子α（TNFα）、白细胞介素18（IL-1β）以及白细胞介素6（IL-6）浓度，胶质细胞表面标记物Toll样受体4（TLR4）、白细胞分化抗原11b（CD11b），胶质纤维酸性蛋白（GFAP）mRNA的表达水平。结果：腰5神经切断后，与Ⅰ组相比各手术组对2g和12g刺激均有明显增多的撤腿反应，但与Ⅱ组相比，Ⅴ组和Ⅵ组对2g和12g刺激的撤腿次数明显减少，Ⅲ组和Ⅳ组则差异无统计学意义（P〉0．05）。术后第7d，与Ⅰ组相比各手术组腰5脊髓TNFα、IL-1β、IL-6及胶质细胞表面标记物TLR-4、CD11b、GFAP的mRNA表达水平明显增高（P〈0．05）。但与Ⅱ组相比，Ⅴ组和Ⅵ组TNFα、IL-1β、IL-6及TLR-4、CD11b、GFAP的mRNA表达水平明显低（P〈0．05），Ⅲ组和Ⅳ组差异则无统计学意义（P〉0．05）。结论：己酮可可碱能够剂量依赖的缓解神经病理性疼痛大鼠痛觉过敏的发展，这与它能减轻脊髓胶质细胞活化、炎症因子表达的效应相关。
Objective： To observe the impact of preventive intraperitoneal administration of pentoxiflylline on the development of mechanical allodynia, the activation of glial cells and the expression of proinflammatory cytokines in the spinal cord of the L5 segment in rats receiving L5 spinal nerve transection. Methods： Forty-eight male SD rats were randomly allocated to 6 groups： group [ （sham operation）, group Ⅱ （ saline control） and group Ⅲ-Ⅵ （ 12.5, 25, 50 and 100 mg/kg pentoxifylline respectively）. The rat 15 spinal nerve transection model of neuropathic pain was applied in our experiment. One hour before surgery, saline was administered intraperitoneally in group Ⅰ and Ⅱ , while the respective doses of pentoxifylline used in group Ⅲ- Ⅵ. Furthermore, the same doses were given at 16 o＇clock 1 -6 d after surgery. The number of withdrawals elicited by the stimuli of 2 g or 12 g yon Frey filament on the dorsal surface of the ipsilateral hind paw was recorded before surgery and on day 1, 4 and 7 after nerve transection. After behavioral testing on post-surgical day 7, the rats were euthanized and the spinal cord of the I5 segment collected to analyze the level of proinflammatory cytokines, such as TNFα （ Tumor necrosis factor α）, IL-1β （ Interleukin 1 β） and IL-6, as well as the expression of mRNA of such glial cell surface markers as TLR-4 （Toll-like receptor 4 ）, CD11b （Cluster of differentiation antigen 11b） and GFAP （ Glial fibrillary acidic protein）. Results ： After L5 spinal nerve transection, the number of paw withdrawals was significantly increased in the nerve injury groups compared with group Ⅰ, markedly decreased in group Ⅴ and Ⅵ compared with group Ⅱ , and showed no statistically significant difference between group Ⅲ and Ⅳ. On post surgical day 7, the level of TNFα, IL-1β and IL-6, as well as the mRNA expression of TLR-4, CD11 b and GFAP in the spinal cord of the L5 segment were significantly elevated in nerve transection groups compared with group Ⅰ , but were obviously lower in group Ⅴ and Ⅵ than in group Ⅱ , with no significant difference between group Ⅲ and Ⅳ. Conclusion： Pentoxifylline could dose-dependently attenuate the development of allodynia in rats with neuropathic pain, which may be attributed to its action of alleviating the activation of glia and suppressing the expression of proinflammatory cytokines.
出处
《医学研究生学报》
CAS
2009年第1期24-27,共4页
Journal of Medical Postgraduates
基金
南京军区医学科学技术研究"十一五"计划重点课题(批准号:06Z39)
