PM2.5对哮喘大鼠IL-17/IL-23炎症介质的影响及人参皂苷Rg1干预研究

周亚兵 蒋思韵 王利维 华丽

摘要 目的：基于气道IL-17/IL-23炎症介质轴，探讨人参皂苷Rg1对PM2.5哮喘大鼠肺损伤保护机制。方法：采集并分离交通相关大气细颗粒物PM2.5，利用卵白蛋白致敏和激发建立幼龄哮喘大鼠模型，再给予PM2.5气管滴注建立PM2.5哮喘肺损伤模型，采用酶联免疫吸附试验（ELISA）法测定血清和肺泡灌洗液IL-17a、IL-6、IL-23、TGF-β1含量，RT-PCR检测RORγt mRNA表达，并行肺组织病理和电镜分析。结果：成功建立PM2.5气管滴注哮喘大鼠模型;哮喘大鼠模型血清和肺泡灌洗液IL-17a、IL-6、IL-23、TGF-β1表达量增大（P<0.01），肺组织RORγt mRNA表达量增加（P<0.01）;经PM2.5气管滴注后，模型组大鼠血清和肺泡灌洗液IL-17a、IL-6、IL-23、TGF-β1含量进一步增加，RORγt mRNA表达量进一步上升（P<0.01）;经皂苷Rg1干预后，呈现剂量依赖性下调血清和肺泡灌洗液IL-17a、IL-6、IL-23、TGF-β1水平，下调RORγt mRNA表达量。结论：人参皂苷Rg1呈剂量依赖性改善PM2.5致哮喘大鼠肺气道炎症反应、改善肺损伤。

关键词 哮喘;大气颗粒物2.5;辅助性T细胞17;白细胞介素-17;白细胞介素-23;维A酸相关孤儿受体γt;人参皂苷Rg1

Abstract Objective：Based on the airway IL-17/IL-23 inflammatory factor axis，to explore the protective mechanism of Ginsenoside Rg1 on lung injury in PM2.5 asthmatic rats.Methods：PM2.5 was isolated and sensitized by ovalbumin，and then PM2.5 was intratracheal instilled to establish PM2.5 asthmatic lung injury model.The levels of IL-17a，IL-6，IL-23 and TGF-β1 in serum and BALF were measured by ELISA.The expression of RORγt mRNA was detected by RT-PCR，and the lung tissue pathology and electron microscopy were analyzed.Results：The asthmatic rat model of PM2.5 was established successfully; The expression of IL-17a，IL-6，IL-23 and TGF-β1 in serum and BALF of asthmatic rats increased（P<0.01），and the expression of RORγt mRNA in lung tissue increased（P<0.01）; After PM2.5 intratracheal instillation，the contents of IL-17a，IL-6，IL-23 and TGF-β1 in serum and BALF of model group were further increased，and the expression of RORγt mRNA was further increased（P<0.01）;After intervention with saponin Rg1，IL-17a，IL-6，IL-23，TGF-β1 in serum and BALF were decreased in a dose-dependent manner，and RORγt mRNA expression was down regulated.Conclusion：Ginsenoside Rg1 can improve airway inflammation and lung injury induced by PM2.5 in a concentration dependent manner.

Keywords Asthma; atmospheric particulate matter 2.5; helper T cell 17; IL-17;IL-23;retinoic acid related orphan receptor γt; ginsenoside Rg1

中圖分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.10.004

大气颗粒物PM2.5（Particulate Matter 2.5），因其粒径小、比表面积大、组成复杂，易富集有毒有害物质，随呼吸可进入肺泡深部，甚至透过呼吸膜进入循环系统[1]。研究已证实PM2.5与呼吸、心脑血管及免疫系统的疾病关系密切，儿童机体发育尚未完善，更易受到PM2.5的危害[2-4]，导致肺组织结构损伤和功能缺陷，影响肺功能，导致儿童哮喘患病率和症状严重程度增加[5-7]。Th17作为重要炎症细胞，在多种炎症反应疾病中发挥重要作用;IL-23具有激活记忆T细胞向Th17细胞转化的功能;维A酸相关孤儿受体γt（Retinoid Acid-related Orphan Receptor Gamma t，RORγt）是Th17细胞分化的关键核因子及Th17细胞谱系特异性转录激活因子，可诱导调控IL-17高水平分泌，诱导多种细胞释放炎症介质而导致过度炎症反应，从而促进哮喘发病[8]。人参皂苷Rgl（Ginsenoside-Rgl，G-Rgl）具有抗氧化应激、抗炎症反应、抗纤维化和神经保护作用[9]，对脓毒症肺损伤有修复作用[10]，那么，皂苷Rg1对PM2.5损伤哮喘大鼠肺气道是否有修复保护作用？……