赵会超, 王静, 吴红燕, 张志红. 交通相关PM2.5及其不同成分对哮喘大鼠Th17细胞和相关细胞因子的影响[J]. 环境与职业医学, 2019, 36(5): 438-444. DOI: 10.13213/j.cnki.jeom.2019.18748
引用本文: 赵会超, 王静, 吴红燕, 张志红. 交通相关PM2.5及其不同成分对哮喘大鼠Th17细胞和相关细胞因子的影响[J]. 环境与职业医学, 2019, 36(5): 438-444. DOI: 10.13213/j.cnki.jeom.2019.18748
ZHAO Hui-chao, WANG Jing, WU Hong-yan, ZHANG Zhi-hong. Effects of traffic related PM2.5 and its components on Th17 cells and related cytokines in asthmatic rats[J]. Journal of Environmental and Occupational Medicine, 2019, 36(5): 438-444. DOI: 10.13213/j.cnki.jeom.2019.18748
Citation: ZHAO Hui-chao, WANG Jing, WU Hong-yan, ZHANG Zhi-hong. Effects of traffic related PM2.5 and its components on Th17 cells and related cytokines in asthmatic rats[J]. Journal of Environmental and Occupational Medicine, 2019, 36(5): 438-444. DOI: 10.13213/j.cnki.jeom.2019.18748

交通相关PM2.5及其不同成分对哮喘大鼠Th17细胞和相关细胞因子的影响

Effects of traffic related PM2.5 and its components on Th17 cells and related cytokines in asthmatic rats

  • 摘要: 背景 Th17细胞在一些自身免疫性疾病发生过程中发挥着重要作用,其可通过分泌特征性细胞因子白介素(IL)-17发挥强致炎作用,并依靠IL-23维持扩增存活状态。

    目的 本研究探讨交通相关PM2.5及其水溶、有机成分对哮喘大鼠亚急性染毒后,Th17细胞及其相关细胞因子在加重哮喘发作中的作用。

    方法 选择80只体重180~220 g的SD雄性大鼠,随机分为8组,每组10只,分别为生理盐水对照组、哮喘对照组、PM2.5染毒组、低水溶成分染毒组、高水溶成分染毒组、DMSO对照组、低有机成分染毒组、高有机成分染毒组。各染毒组用卵清蛋白(OVA)致敏,以OVA进行雾化激发建立大鼠哮喘模型,激发阶段气管滴注PM2.5及其水溶、有机成分,构建哮喘加重模型。分析大鼠脏器系数变化,检测大鼠支气管肺泡灌洗液(BALF)中白细胞总数和细胞分类计数;ELISA法检测大鼠BALF中IL-17及IL-23的表达水平,流式细胞计数法检测大鼠外周血中Th17细胞比例。

    结果 经OVA致敏激发后,哮喘模型大鼠均出现明显的直立喘息、呼吸急促、前肢缩抬、抓脸等哮喘症状,而生理盐水对照组大鼠无上述症状。PM2.5染毒组及高水溶成分染毒组中左肺脏器系数升高,与哮喘对照组间差异有统计学意义(均P < 0.05)。PM2.5及其水溶、有机成分均可引起BALF中白细胞总数升高,PM2.5水溶和有机成分均可以引起嗜酸性粒细胞百分比升高与巨噬细胞百分比降低,PM2.5水溶成分可单独引起中性粒细胞百分比升高(均P < 0.05)。PM2.5水溶和有机成分高剂量染毒组IL-17表达量(66.04±12.70)、(57.95±7.25)pg/mL)高于其低剂量染毒组(45.32±12.66)、(39.35±6.47)pg/mL)(均P < 0.05);对比PM2.5水溶、有机成分染毒组,PM2.5引起更高的IL-23(304.78±86.08)pg/mL)表达(均P < 0.05)。PM2.5水溶和有机成分高剂量染毒组Th17细胞百分比(3.76±1.44)%、(4.41±1.55)%)高于其低剂量染毒组(2.18±0.84)%、(2.06±0.63)%)、哮喘对照组(1.79±0.26)%)、DMSO对照组(1.33±0.81)%)(均P < 0.05)。

    结论 研究显示PM2.5全颗粒物及其水溶、有机成分均可以通过升高Th17细胞比例并高表达IL-17、IL-23加重哮喘发作。PM2.5水溶成分对肺脏毒性作用强于PM2.5有机成分,且PM2.5在介导Th17加重哮喘发作中的作用强于其单一成分的作用。

     

    Abstract: Background Th17 lymphocytes play an important role in the development of some autoimmune diseases by secreting the characteristic cytokine IL-17 to exert their strong inflammatory effects and relying on IL-23 for expansion and maintenance.

    Objective This study is to investigate the role of Th17 lymphocytes and related cytokines in an asthmatic rat model exacerbated by subacute exposure to traffic related PM2.5 and its aqueous and organic extracts.

    Methods Eighty SD rats weighing 180-220 g were randomly divided into eight groups, with 10 rats in each group, including saline control group, asthma control group, PM2.5 group, low-dose aqueous extract group (low AE group), high-dose aqueous extract group (high AE group), DMSO control group, low-dose organic extract group (low OE group), and high-dose organic extract group (high OE group). All the exposed groups were sensitized with ovalbumin (OVA) and challenged with aerosolized OVA to establish an asthmatic rat model. PM2.5 and its aqueous and organic extracts were intratracheally instilled into the asthmatic rats during the challenge phase to construct an asthmatic exacerbation rat model. Changes of organ coefficients and total and differential white blood cells in bronchoalveolar lavage fluid (BALF) were calculated. The expression levels of IL-17 and IL-23 in BALF were determined by ELISA. The percentages of Th17 cells in peripheral blood were measured by flow cytometry.

    Results After OVA sensitization and challenge, the asthmatic rats showed obvious symptoms of wheezing, shortness of breath, forelimb contraction, and scratching face, while the rats in the saline control group had no such symptoms. The left lung coefficients of the PM2.5 group and the high AE group were significantly higher than that of the asthma control group (Ps < 0.05). PM2.5 and its aqueous or organic components induced elevated white blood cells; PM2.5 aqueous and organic extracts led to increased eosinophil percentage and decreased macrophage percentage; PM2.5 aqueous extracts resulted in elevated neutrophil percentage (Ps < 0.05). The expression levels of IL-17 in BALF of the high AE and OE groups(66.04±12.70), (57.95±7.25) pg/mL were both higher than those of the low AE and OE groups(45.32±12.66), (39.35±6.47)pg/mL (Ps < 0.05); PM2.5 induced a higher IL-23 expression level(304.78±86.08)pg/mL than any PM2.5 AE or OE groups (Ps < 0.05). The percentages of Th17 cells in the high AE and OE groups(3.76±1.44)%, (4.41±1.55)% were significantly higher than those of the low AE and OE groups(2.18±0.84)%, (2.06±0.63)%, the asthma control group(1.79±0.26)%, and the DMSO control group(1.33±0.81)% (Ps < 0.05).

    Conclusion The study have demonstrated that PM2.5 and its aqueous and organic extracts aggravate asthma attacks by increasing the proportion of Th17 lymphocytes and up-regulating the expressions of IL-17 and IL-23. PM2.5 aqueous extracts have stronger toxicity to the lung than its organic extracts, and PM2.5 plays a more potent role in mediating exacerbation of asthma attacks by Th17 than its individual extracts.

     

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