基础医学与临床 ›› 2016, Vol. 36 ›› Issue (11): 1517-1524.

• 研究论文 • 上一篇    下一篇

肉毒毒素A对大鼠慢性神经源性疼痛中P物质和炎性反应的影响

陈彦强1,王永平2,杨同群1,周斌1,张海鸿1   

  1. 1. 兰州大学第二医院
    2. 临夏州人民医院
  • 收稿日期:2015-08-25 修回日期:2016-03-31 出版日期:2016-11-05 发布日期:2016-10-24
  • 通讯作者: 张海鸿 E-mail:zhoubing029@126.com

Effect of botulinum toxin type A on substance P and inflammation of rats with chronic neurogenic pain

  • Received:2015-08-25 Revised:2016-03-31 Online:2016-11-05 Published:2016-10-24

摘要: 目的 探索肉毒毒素A(BoNT-A)对慢性神经源性疼痛的镇痛效应和作用机制。方法 将大鼠随机分为对照组、假手术组、疼痛模型组(结扎左侧L5、L6脊神经,结扎3 d后于同侧足底皮下注射0.9% NaCl溶液)、肉毒毒素干预组(结扎左侧L5、L6脊神经,结扎3 d后同侧足底皮下注射BoNT-A 30U/kg)。根据处死时间不同将各组分为1d、3d和1周(1w)组。HE染色观察组织形态学变化,免疫组化检测P物质(SP)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF-α)蛋白表达情况,原位杂交及实时定量PCR法测定其基因表达水平。结果 SNL后大鼠脊髓炎性细胞浸润,并随着结扎时间的增长浸润程度加重。与对照组比较,疼痛模型组1d、3d和1w时SP、IL-6和TNF-α的蛋白、mRNA表达均显著上升(P<0.05);与疼痛模型组比较,肉毒毒素干预组1d、3d和1w时SP、IL-6和TNF-α的蛋白、mRNA表达均显著下降(P<0.05)。结论 BoNT-A对慢性神经源性疼痛的镇痛机制可能是通过抑制神经递质SP和炎性介质IL-6、TNF-α的表达实现的。

关键词: 慢性神经源性疼痛, 肉毒毒素A, P 物质, IL-6, TNF-α

Abstract: Objective To explore the influence and mechanism of botulinum toxin A on chronic neurogenic pain.Methods Wistar rats were randomly divided into control group, sham group,pain model group (the left L5 and L6 nerves of rats were ligated,after 3 daythe left was injected with normal saline from ipsilateral plantar subcutaneous.) and botulinum toxin treatment group (the left L5 and L6 nerves of rats were ligated, after 3 day the left was injected with 30U/kg BoNT-A from ipsilateral plantar subcutaneous). The botulinum toxin treatment group was further divided into 1d, 3d and 1w group according to the execution time. The cell morphology changes were observed by HE staining.The protein and mRNA expression levels of substance P (SP),interleukin6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by immunohistochemical method,in-situ hybridization and real-time quantitative PCR.Results HE staining showed spinal cord inflammatory cells infiltration after SNL rats. Inflammatory infiltration degree was aggravated in the spinal cord as the extension of the ligation time.Protein and mRNA expression levels of SP, IL-6 and TNF-α were significantly higher in pain model 1d,3d and 1w group than that incontrol group (P<0.05).But those were lower in botulinum toxin treatment group at 1d,3d and 1w than that inpain model group (P<0.05) as determined by immunohistochemistry,in-situ hybridization and real-time quantitative PCR.Conclusions Neurotransmitter SP and inflammatory mediators IL-6 and TNF-α were involved in the analgesic effect of BoNT-A on chronic neurogenic pain.