摘要
目的探讨神经妥乐平(NTP)对白蛋白结合型紫杉醇(Nab-PTX)诱导的神经病理性疼痛的作用及其机制。方法将40只SD大鼠随机分为对照组、Nab-PTX组、Nab-PTX联合NTP组(Nab-PTX+NTP组)和Nab-PTX联合核因子κB抑制剂PDTC组(Nab-PTX+PDTC组),检测4组大鼠机械缩足反射阈值(MWT)和热缩足潜伏期(TWL)。取各组大鼠L4~6脊髓组织,通过酶联免疫吸附试验检测炎性细胞因子肿瘤坏死因子α(TNF-α)和白细胞介素-6(IL-6)的表达水平;免疫荧光染色检测小胶质细胞活化情况;实时PCR和Western blotting分别检测TLR4、p65 mRNA和蛋白表达水平。结果Nab-PTX诱导大鼠出现神经病理性疼痛,表现为MWT、TWL下降;NTP和PDTC均能减轻Nab-PTX诱导的神经病理性疼痛,减少MWT、TWL下降幅度。与对照组相比,Nab-PTX组TNF-α、IL-6、Iba-1水平升高,TLR4、p65 mRNA和蛋白表达水平升高(P<0.05)。与Nab-PTX组相比,Nab-PTX+NTP组和Nab-PTX+PDTC组TNF-α、IL-6、Iba-1水平降低,TLR4、p65 mRNA和蛋白表达水平降低(P<0.05)。结论NTP能够通过抑制TLR4/NF-κB信号通路减轻大鼠炎症反应,进而减轻Nab-PTX诱导的神经病理性疼痛。
Objective To investigate the effect and mechanism of action of neurotropin(NTP)on neuropathic pain induced by albumin-bound paclitaxel(Nab-PTX).Methods Forty SD rats were randomly divided into the control,Nab-PTX,Nab-PTX+NTP,and Nab-PTX+PDTC groups.The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured in each group of rats.The L4-6 spinal cord tissues of rats in each group were sampled.The expression of inflammatory cytokines was detected by enzyme-linked immunosorbent assay,microglial activation by immunofluorescence staining,and the expression of TLR4 and p65 mRNA and protein by real-time PCR and Western blotting,respectively.Results Nab-PTX induced neuropathic pain in rats,which manifested as a decrease in MWT and TWL.Both NTP and PDTC alleviated Nab-PTX-induced neuropathic pain and antagonized the magnitude of decrease in MWT and TWL.Compared with the control group,the levels of TNF-α,IL-6,and Iba-1,and expressions of TLR4 and p65 mRNA and protein were increased in the Nab-PTX group(P<0.05).Compared with the Nab-PTX group,the levels of TNF-α,IL-6 and Iba-1 lower in the Nab-PTX+NTP and Nab-PTX+PDTC groups,and the expressions of TLR4 and p65 mRNA and protein were decreased(P<0.05).Conclusion Neurotropin can attenuate inflammatory response in rats by inhibiting the TLR4/NF-κB signaling pathway,thereby reducing Nab-PTX-induced neuropathic pain.
作者
刘梦莹
刘淑娟
高鹏飞
刘彩霞
窦佳
都兰
王薇
LIU Mengying;LIU Shujuan;GAO Pengfei;LIU Caixia;DOU Jia;DU Lan;WANG Wei(Graduate School of Inner Mongolia Medical University,Hohhot 010059,China;The Fourth Department of Oncology,Mudanjiang Tumor Hospital,Mudanjiang 157000,China;Department of Oncology,Arun Banner People’s Hospital,Arun Banner 162750,China;Department of Oncology,The Affiliated Tumor Hospital of Inner Mongolia Medical University,Hohhot 010050,China)
出处
《中国医科大学学报》
北大核心
2026年第2期133-138,共6页
Journal of China Medical University
基金
内蒙古自治区卫生健康科技计划(202202191)
内蒙古医科大学联合项目(YKD2023LH054)。
