白蛋白结合型紫杉醇诱导大鼠神经病理性疼痛的作用机制  

Effects and mechanism of albumin-bound paclitaxel-induced neuropathic pain in rats

作　　者：陈秀兰 刘淑娟 苏乌云[2] 闫海成[3] 窦佳 李志伟 王薇[2] CHEN Xiulan;LIU Shujuan;SU Wuyun;YAN Haicheng;DOU Jia;LI Zhiwei;WANG Wei(Graduate School of Inner Mongolia Medical University,Huhhot 010107,China;Department of Oncology,Affiliated Hospital of Inner Mongolia Medical University,Huhhot 010051,China;Department of Neurosurgery,Affiliated Hospital of Inner Mongolia Medical University,Huhhot 010051,China;Department of Internal Medicine,The Second People’s Hospital of Etuoke Banner,Inner Mongolia Etuoke Banner 016064,China)

机构地区：[1]内蒙古医科大学研究生学院,呼和浩特010107 [2]内蒙古医科大学附属医院肿瘤内科,呼和浩特010051 [3]内蒙古医科大学附属医院神经外科,呼和浩特010051 [4]内蒙古鄂托克旗第二人民医院急诊科,内蒙古鄂托克旗016064

出　　处：《中国医科大学学报》2022年第12期1102-1108,1115,共8页Journal of China Medical University

基　　金：内蒙古自治区自然科学基金(2020LH08035);希思科-石药肿瘤研究基金(Y-sy2018-134);北京科创医学发展基金会(KC2021-JX-0044-9)。

摘　　要：目的 探讨白蛋白结合型紫杉醇(Nab-PTX)诱导大鼠神经病理性疼痛的作用机制。方法 构建Nab-PTX诱导的神经病理性疼痛大鼠模型,随机分为Nab-PTX 4 mg/kg组、Nab-PTX 6 mg/kg组及对照组(生理盐水组),每组10只。通过行为学测试检测大鼠机械缩足反射阈值(PWMT)及热缩足反射潜伏期(PWTL);大鼠PWMT最低值时在脊髓腰膨大处取材,ELISA检测炎性细胞因子的表达;免疫荧光染色检测小胶质细胞和星形胶质细胞标志物(Iba-1和GFAP)的激活情况;实时PCR和Western blotting检测Toll样受体4/核因子-κB p65 (TLR4/NF-κB p65)的mRNA及蛋白表达情况。结果 成功构建Nab-PTX诱导的神经病理性疼痛大鼠模型,结果显示肿瘤坏死因子α、白细胞介素-6和白细胞介素-1β表达均上调(P <0.05),而白细胞介素-10表达水平无统计学差异;Iba-1和GFAP均明显的增殖和活化;TLR4及下游信号NF-κB p65的mRNA及蛋白表达均增加(P <0.05)。结论 Nab-PTX诱导的大鼠神经病理性疼痛机制可能与脊髓小胶质细胞和星形胶质细胞激活、TLR4/NF-κB p65信号通路上调及炎性细胞因子的分泌增加有关。Objective To investigate the effects and mechanism of albumin-bound paclitaxel(Nab-PTX)-induced neuropathic pain in rats. Methods A rat model of neuropathic pain induced by Nab-PTX was randomly divided into the following groups:Nab-PTX 4 mg/kg,Nab-PTX 6 mg/kg,and control(n = 10 each). The paw withdrawal mechanical threshold(PWMT) and paw withdrawal thermal latency of rats were detected by a behavioral test. Samples were collected from lumbar enlargements of the spinal cord when the lowest PWMT value was measured,and the expression of inflammatory cytokines was detected by ELISA. The inflammatory activation of microglia and astrocyte markers(Iba-1 and GFAP) was assessed by immunofluorescence staining. The mRNA and protein expression of Toll-like receptor 4(TLR4)/nuclear factor-κBp65(NF-κBp65) were detected by real-time PCR and Western blotting. Results The rat model of Nab-PTXinduced neuropathic pain was successfully established. The expression of TNF-α,IL-6,and IL-1β was upregulated,but there was no significant difference in the expression of IL-10. The proliferation and activation of Iba-1 and GFAP were detected,and the mRNA and protein expression of TLR4 and downstream signal NF-κBp65 were found to be increased. Conclusion The mechanism underlying NabPTX-induced neuropathic pain in rats may be related to the activation of spinal microglia and astrocytes,upregulation of TLR4/NF-κBp65signaling pathway and increased secretion of inflammatory cytokines.

关 键 词：白蛋白结合型紫杉醇 神经病理性疼痛 Toll样受体4/核因子-κB p65 小胶质细胞 星形胶质细胞 炎性细胞因子 

分 类 号：R73.3[医药卫生—肿瘤]