没食子酸通过调控NLRP3炎症体通路缓解紫杉醇所致神经炎症的研究  

Gallic Acid Alleviates Paclitaxel-Induced Neuroinflammation through Regulation of the NLRP3 Inflammasome Pathway

作　　者：陈阳 陈佳怡 朱静 CHEN Yang;CHEN Jiayi;ZHU Jing(Department of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学药学院,江苏南京210023

出　　处：《南京中医药大学学报》2024年第11期1178-1188,共11页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(82174295)。

摘　　要：目的探究没食子酸(Gallic acid,GA)对紫杉醇所致周围神经病变的保护作用及机制。方法提取原代背根神经节(DRG)建立体外紫杉醇诱导的DRG细胞损伤模型,CCK-8法检测细胞活力探究没食子酸对该模型是否具有神经保护作用。建立紫杉醇诱导的C57BL/6J小鼠神经病理性疼痛模型,通过行为学测试研究没食子酸能否缓解紫杉醇所致外周神经病变导致的神经病理性疼痛,探究没食子酸是否通过抑制由紫杉醇引起的NLRP3炎性小体活化,减少促炎细胞因子释放,缓解紫杉醇引起的周围神经病理性疼痛。通过qPCR检测DRG细胞中NLRP3、Caspase-1、IL-1βmRNA表达水平;Western blot检测NLRP3、Caspase-1、IL-1β蛋白表达水平;免疫荧光染色分析NLRP3、Caspase-1、IL-1β荧光强度。结果没食子酸对由紫杉醇诱导损伤的DRG细胞模型具有保护作用,提高了DRG细胞的存活率;并减轻了PIPN小鼠由紫杉醇引起的冷痛、热痛和机械痛觉超敏反应;没食子酸有效逆转了由紫杉醇引起的DRG细胞中NLRP3、Caspase-1的表达水平升高,减少促炎细胞因子IL-1β的释放。结论没食子酸通过调控NLRP3炎症体通路,改善了紫杉醇所诱导的神经炎症反应。OBJECTIVE To explore the protective effect and mechanism of gallic acid(GA)on paclitaxel-induced peripheral neuropathy.METHODS The primary dorsal root ganglion(DRG)was extracted to establish an in vitro model of paclitaxel-induced DRG cell injury;CCK-8 assay was used to evaluate the neuroprotective effects of GA on this model.The paclitaxel-induced neuropathic pain model in C57BL/6J mice was established,and the behavioral test was used to analyze effects of GA alleviating paclitaxel-induced peripheral neuropathy and to explore whether GA alleviated paclitaxel-induced peripheral neuropathic pain by inhibiting the activation of NLRP3 inflammatory and reducing the release of pro-inflammatory cytokine.qPCR was used to detect the expression levels of NLRP3,Caspase-1,and IL-1βmRNA in DRG cells;Western blot was used to detect the change of protein levels of NLRP3,Caspase-1,and IL-1β;and the fluorescence intensity of NLRP3,Caspase-1,and IL-1βproteins was analyzed by immunofluorescence staining.RESULTS GA exerts a protective effect and improved the survival rate of paclitaxel-stimulated DRG cells;reduced mechanical,cold and thermal pain hyperalgesia in mice;effectively reversed the elevated expression levels of NLRP3 and Caspase-1 in paclitaxel-stimulated DRG cells and reduced the release of pro-inflammatory cytokine IL-1β,which ameliorated the neuroinflammatory response induced by paclitaxel.CONCLUSION Gallic acid improves paclitaxel-induced neuroinflammation by regulating the NLRP3 inflammasome pathway.The NLRP3/Caspase-1/IL-1βpathway is one of the potential mechanisms for the treatment of paclitaxel-induced peripheral neuropathy.

关 键 词：紫杉醇 没食子酸 NLRP3炎症小体 外周神经损伤 神经炎症 

分 类 号：R285.5[医药卫生—中药学]