摘要
目的探索肉毒毒素A(Bo NT-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%氯化钠溶液)、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Bo NT-A 30 U/kg)。根据处死时间不同将各组分为1 d、3 d和1周(1 w)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1 d、3 d和1周时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1 d、3 d和1周时SP、IL-6和TNF-α的蛋白、mRNA表达均显著下降(P<0.05)。结论 Bo NT-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。
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 L6nerves of rats were ligated,after 3 day the left side was injected with normal saline from ipsilateral plantar subcutaneous.） and botulinum toxin treatment group（ the left L5 and L6nerves of rats were ligated,after 3 day the left side was injected with 30 U / kg Bo NT-A from ipsilateral plantar subcutaneous）. The botulinum toxin treatment group was further divided into 1 d,3 d and 1 week 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）,interleukin 6（ IL-6） and tumor necrosis factor-α（ TNF-α） were detected by immunohistochemical method,in situhybridization and real-time quantitative PCR. Results Inflammatory infiltration degree was aggravated in the spinal cord as the extension of the ligation time. Protein and mRNA expression of SP,IL-6 and TNF-α were significantly higher in pain model 1 d,3 d and 1 week group than that in control group（ P〈0. 05）. But those were lower in botulinum toxin treatment group at 1 d,3 d and 1 week than that in pain 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 are involved in the analgesic effect of Bo NT-A on chronic neurogenic pain.
出处
《基础医学与临床》
CSCD
2016年第11期1517-1524,共8页
Basic and Clinical Medicine
基金
甘肃省第七批科技计划(自然科学基金)(1107RJZA140)
