不同给药途径下葛根素对坐骨神经分支选择性损伤小鼠机械痛阈及促炎症因子表达的影响

Effects of different routes of administration of Puerarin on mechanical pain threshold and expression of inflammatory factors in spared sciatic nerve injury mice

目的探索不同给药方式下葛根素对坐骨神经分支选择性损伤模型小鼠机械痛阈及促炎症因子表达的影响。方法将40只BALB/c小鼠随机分为正常对照组(CON组),坐骨神经分支选择性损伤建模无治疗组(SNI组)、模型鼠腹腔注射葛根素组、模型鼠鞘内注射葛根素组、模型鼠鞘内置管注射葛根素组、模型鼠鞘内注射生理盐水组、正常鼠鞘内注射生理盐水组、正常鼠鞘内注射葛根素组。观察各组小鼠行为学变化,测定小鼠患侧足部机械痛阈,计算50%机械缩足反应阈值(50%MWT);分别收集CON组、SNI组建模7 d、给予葛根素或生理盐水处理7 d的其余组小鼠L~L节段的患侧脊髓背角,采用RT-qPCR检测其中促炎症因子IL-1β、IL-6、TNF-α mRNA的表达水平。结果模型鼠50%MWT在腹腔注射葛根素前后无明显变化,在鞘内注射及鞘内置管给药后较给药前明显上升(均P<0.05);模型鼠患侧脊髓IL-1β、IL-6、TNF-α mRNA表达水平在建模后明显上升(均P<0.05),鞘内注射葛根素7 d较给药前进一步上升(均P<0.05),鞘内置管注射葛根素7 d较给药前明显下降(均P<0.05)。结论外周腹腔注射葛根素对SNI小鼠机械痛阈无明显作用,反复鞘内注射有致无菌性炎症风险,鞘内置管方式是发挥葛根素对神经病理性疼痛治疗作用的有效途径。

Objective To investigate the effects of different administration methods of puerarin on mechanical pain threshold and expression of inflammatory factors in mice with spared sciatic nerve injury.Methods Forty BALB/c mice were randomly divided into normal control group(CON group),spared sciatic nerve injury group without treatment(SNI group),model mice intraabdominal injection of puerarin group,model mice intrathecal injection of puerarin group,model mice intrathecal catheterization of puerarin group,model mice intrathecal injection of saline group,normal mice intrathecal injection of saline group and normal mice intrathecal injection of puerarin group.The behavioral changes of every groups were observed,the mechanical pain threshold of mice was measured,and the 50% mechanical withdraw threshold(50% MWT)was calculated.The dorsal horns of the affected spinal cord(L-Lsegments)of mice in the CON group,the SNI group(7 d after modeling)and the remaining groups(7 d after administration of Puerarin or normal saline)were collected,and the levels of inflammatory factors IL-1β,IL-6 and TNF-α mRNA were detected by RT-qPCR.Results The 50% MWT of SNI mice treated by intrathecal injection of puerarin had no significant change after administration.The 50%MWT of SNI mice increased significantly after intrathecal injection and intrathecal catheterization of puerarin(allP<0.05).The levels of IL-1β、IL-6 and TNF-α mRNA in the spinal cord of SNI mice increased significantly after modeling(allP<0.05).The inflammatory factor on the 7 d after intrathecal injection of puerarin were further higher than those before administration(allP<0.05),and the inflammatory factor on the 7 d after intrathecal catheterization of puerarin were significantly lower than those before administration(allP<0.05).Conclusions Intraabdominal injection of puerarin have no significant effect on pain threshold in SNI mice.Repeated intrathecal injection could cause aseptic inflammation.The intrathecal catheterization is an effective way to exert the therapeutic effect of puerarin on neuropathic pain.