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P38 MAPK抑制剂对神经病理性疼痛大鼠脊髓TNF-α合成的影响 被引量:8

P38 MAPK inhibitor decreases the TNF-α level in spinal cord of rats with chronic constriction Injury
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摘要 目的通过建立坐骨神经慢性压迫损伤模型,研究P38丝裂原激活蛋白激酶(P38 MAPK,P38)与TNF-α在神经病理性疼痛发生与发展中的相互作用。方法 SD大鼠分5组:1)空白对照组,2)假手术组,3)CCI手术未治疗组,4)CCI手术0.9%氯化钠注射液治疗组,5)CCI手术SB203580(P38抑制剂)治疗组。上述治疗组中,0.9%氯化钠注射液或SB203580分别于术前1天、术后第1和第7天鞘内注射。各组大鼠分别于术后3、7和14 d测定机械痛阈。采用Western blot和免疫组化方法测定脊髓中TNF-α含量及P38活化水平。结果与假手术组相比,CCI手术后3、7和14 d磷酸化P38(p-P38)水平分别增加275%±65%、267%±66%和253%±56%(P<0.05)。外周神经损伤后引起机械性触诱发痛,并且使脊髓中TNF-α浓度增加,与对照组相比术后3、7和14 d时TNF-α浓度分别增加93%±22%、73%±25%和52%±15%(P<0.05)。预先或术后立即给予SB203580抑制P38活化可以减少脊髓TNF-α合成,使其降至接近对照组水平,从而有效缓解病理性疼痛。结论外周神经损伤后,作为信号传导通路之一的P38可能通过促进脊髓TNF-α合成,引发神经病理性疼痛。 Objective To prove the hypothesis that chronic constrictive injury(CCI) of the sciatic nerve could promote spinal cord release of TNF-α and produce allodynia via the P38 MAPK pathway.MethodsSD rats were divided into five groups: 1)control rats,2)sham surgery rats,3)CCI surgery rats without treatment,4)CCI surgery rats with saline treatment,and 5) CCI surgery rats with the P38 inhibitor SB203580 treatment.In treatment groups,saline or SB203580 was given intrathecally starting 1 day before or 1 day or 7 days after CCI.All rats were killed at different times after surgery to examine P38 activity and TNF-α levels in the spinal cord by Western blot analysis or immunohistochemistry.Mechanical allodynia was tested by a series of von Frey hairs 3,7,and 14 days after surgery.Results p-P38 level was significantly increased at 3 d(275%±65%),7 d(267%±66%),and 14 d(253%±56%) after CCI surgery compared with time-matched shams(P0.05).Peripheral nerve injury induced mechanical allodynia and enhanced spinal concentrations of TNF-α.Pretreatment or early treatment with SB203580 inhibited P38 activity,resulting in the reduction of TNF-α synthesis and the attenuation of mechanical allodynia.Conclusions P38 activation is a signaling cascade that culminates in TNF-α synthesis and contributes to mechanical allodynia after peripheral nerve injury.
出处 《基础医学与临床》 CSCD 北大核心 2012年第10期1126-1131,共6页 Basic and Clinical Medicine
基金 国家自然科学基金(31070930) 中央保健专项基金(B2009B076)
关键词 神经病理性疼痛 P38 MAPK TNF-Α 脊髓 neuropathic pain P38 MAPK TNF-α spinal
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同被引文献102

  • 1张恒,周占松,刘丽梅,杨忠,宋波.P物质刺激下脊髓星形胶质细胞活化中磷酸化P38丝裂素活化蛋白激酶和c-fos的表达及作用[J].第三军医大学学报,2006,28(21):2163-2166. 被引量:6
  • 2潘雪莲,周青山,杜大萍.丹参酮ⅡA对糖尿病大鼠神经病理性疼痛的影响[J].中华麻醉学杂志,2006,26(8):692-695. 被引量:18
  • 3赵红,姜玉秋,孙钱,孙艳妮,刘风雨,石玉顺,万有.脊神经结扎神经病理痛模型大鼠脊髓星形胶质细胞激活与痛行为的关系[J].中国疼痛医学杂志,2007,13(1):39-42. 被引量:12
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