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Research Article

IRF5调控的CXCL13/CXCR5信号轴在cci诱导的大鼠神经性疼痛中的作用机制

卷 24, 期 7, 2024

发表于: 16 October, 2023

页: [940 - 949] 页: 10

弟呕挨: 10.2174/1566524023666230825120836

价格: $65

摘要

背景：神经性疼痛是慢性的，影响患者的生活。研究表明，IRF5和CXCL13/CXCR5参与神经性疼痛;然而，它们的相互作用是未知的。目的:建立慢性压迫性损伤大鼠神经性疼痛模型。研究IRF5重组慢病毒载体和CXCL13中和抗体在神经性疼痛中的作用机制。因此，疾病治疗的新策略可以得到发展。 方法：CCI大鼠鞘内注射重组慢病毒质粒LV-IRF5(过表达)、LV-SH-IRF5(沉默)和CXCL13中和抗体。测量机械戒断阈值(MWT)和热戒断潜伏期(TWL)。通过酶联免疫吸附试验(ELISA)记录肿瘤坏死因子(TNF)- α、白细胞介素(IL)-1β和IL-6水平。用苏木精-伊红(HE)染色脊髓。采用染色质免疫沉淀(ChIP)和双荧光素酶报告基因法分析IRF5与CXCL13的结合。通过实时定量聚合酶链反应和Western blot检测IRF5、神经元核(NeuN)、CXCL13和CXCR5的表达。 结果：CCI组MWT、TWL值均低于Sham组。CXCL13、CXCR5、IRF5在CCI大鼠中的表达随造模时间的延长而逐渐升高。IRF5沉默抑制CCI大鼠NeuN的表达和腰椎增大，促进MWT和TWL。此外，IRF5沉默抑制了CXCR5和CXCL13基因的表达，下调了炎症因子的表达水平。IRF5直接特异性结合内源性CXCL13启动子，对其进行调控。IRF5过表达加重了cci诱导的大鼠神经性疼痛的疾病表型。CXCL13中和抗体可逆转IRF5过表达效应。 结论：IRF5沉默通过下调疼痛阈值、炎症细胞因子水平和CXCL13/CXCR5信号通路，减轻了CCI大鼠的神经性疼痛。IRF5过表达加重了cci所致大鼠神经性疼痛的疾病参数;然而，通过中和针对CXCL13的抗体，它们被逆转。

关键词: IRF5, CCI, CXCL13, CXCR5，神经性疼痛，慢性压迫性损伤。

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