Lu Chan, Liu Qin, Deng Miaomiao, Liao Hongsen, Yang Xu, Ma Ping
XiangYa School of Public Health, Central South University, Changsha 410078, China.
XiangYa School of Public Health, Central South University, Changsha 410078, China.
Sci Total Environ. 2023 Apr 15;869:161760. doi: 10.1016/j.scitotenv.2023.161760. Epub 2023 Jan 23.
Allergic asthma is a complicated respiratory disease with many concerns. Mounting epidemiological evidence linked temperature (T) and NO with allergic asthma, yet toxicological studies remain scarce. We conducted an in vivo study to explore toxicological evidence in T-NO interaction on allergic asthma, to investigate underlying toxicological mechanisms. 90 male Balb/c mice were randomly and equally divided into 6 groups including saline control, ovalbumin (OVA)-sensitized, OVA + 35 °C, OVA + NO, OVA + 35 °C + NO, and OVA + 35 °C + NO + capsazepine (CZP), adopting treatment for 38 days. We measured pulmonary functions of inspiratory resistance (Ri), expiratory resistance (Re) and airway compliance (Cldyn), serum protein biomarkers, indexes of pulmonary inflammation, histopathological changes and protective effects of CZP. Airway hyperresponsiveness (AHR) was aggravated by high T (35 °C) and NO (5 ppm) co-exposure with a series of aggravating asthmatic symptoms including airway wall thickening, lumen stenosis, goblet cell proliferation, mucus hypersecretion, and subepithelial fibrotic hyperplasia, providing evidence in the toxicological impact of high T-NO interaction. The biomarkers of serum immune functions (Total-IgE, OVA-sIgE and IL-4), pro-inflammation (IL-6 and TNF-α), oxidative stress cytokines (8-OHdG, ROS and MDA), airway resistance (Ri and Re), and TRPV1 expression significantly increased, while IFN-γ, GSH and airway compliance (Cldyn) significantly decreased with co-exposure to high T and NO. We observed that CZP addition significantly ameliorated these toxicological effects and biomarker levels induced by heat-NO interaction. Our results suggest a toxicity of heat-NO interaction on asthma with clear mechanisms, which can be ameliorated by CZP, indicating that both oxidative stress and TRPV1 expression may be primarily responsible for asthma of heat-NO-induced toxicity.
过敏性哮喘是一种复杂的呼吸系统疾病，存在诸多问题。越来越多的流行病学证据将温度（T）和一氧化氮（NO）与过敏性哮喘联系起来，但毒理学研究仍然匮乏。我们进行了一项体内研究，以探索T-NO相互作用对过敏性哮喘的毒理学证据，并研究潜在的毒理学机制。将90只雄性Balb/c小鼠随机等分为6组，包括生理盐水对照组、卵清蛋白（OVA）致敏组、OVA + 35°C组、OVA + NO组、OVA + 35°C + NO组和OVA + 35°C + NO +辣椒素（CZP）组，进行为期38天的治疗。我们测量了吸气阻力（Ri）、呼气阻力（Re）和气道顺应性（Cldyn）的肺功能、血清蛋白生物标志物、肺部炎症指标、组织病理学变化以及CZP的保护作用。高温（35°C）和NO（5 ppm）共同暴露会加重气道高反应性（AHR），并伴有一系列加重哮喘的症状，包括气道壁增厚、管腔狭窄、杯状细胞增殖、黏液分泌过多和上皮下纤维化增生，这为高温-T-NO相互作用的毒理学影响提供了证据。血清免疫功能生物标志物（总IgE、OVA特异性IgE和IL-4）、促炎因子（IL-6和TNF-α）、氧化应激细胞因子（8-羟基脱氧鸟苷、活性氧和丙二醛）、气道阻力（Ri和Re）以及瞬时受体电位香草酸亚型1（TRPV1）表达在高温和NO共同暴露时显著增加，而干扰素-γ（IFN-γ）、谷胱甘肽（GSH）和气道顺应性（Cldyn）显著降低。我们观察到添加CZP可显著改善高温-NO相互作用诱导的这些毒理学效应和生物标志物水平。我们的结果表明，高温-NO相互作用对哮喘具有毒性作用，其机制明确，CZP可改善这种毒性作用，这表明氧化应激和TRPV1表达可能是高温-NO诱导毒性导致哮喘的主要原因。
