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Title: [Effects of iris xanthin on airway inflammation, airway remodeling, and the HMGB1/TLR4/NF-κB pathway in asthmatic young mice].
Author: Li YY, Wang XF, Fu Y, Wang YR.
Journal: Zhongguo Dang Dai Er Ke Za Zhi; 2024 Jun 15; 26(6):639-645. PubMed ID: 38926382.
Abstract:
OBJECTIVES: To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in asthmatic young mice. METHODS: Sixty male BALB/c young mice were randomly assigned into six groups: a blank group, a model group, a dexamethasone group, and low, medium, and high dose groups of iris xanthin, with ten mice per group. Asthma models were induced through intraperitoneal injections of a sensitizing agent [ovalbumin (OVA) 20 μg + aluminum hydroxide gel 2 mg], followed by 4% OVA aerosol inhalation. Lung function was measured using a pulmonary function tester to determine lung volume (LV), resting ventilation per minute (VE), and airway reactivity (Penh value). Hematoxylin-eosin (HE) staining was employed to examine and analyze airway remodeling. The contents of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid were quantified using ELISA. Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis were used to assess the expression of HMGB1/TLR4/NF-κB pathway-related mRNA and proteins in lung tissues. RESULTS: Compared to the model group, the dexamethasone and iris xanthin-treated groups (low, medium, and high doses) exhibited significant increases in LV and VE (P<0.05), with incremental dose-dependent increases observed in the iris xanthin groups. Additionally, Penh values, IL-1β, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, and NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were all reduced (P<0.05) in a dose-dependent manner. When compared to the dexamethasone group, the low and medium dose iris xanthin groups showed decreases in LV and VE (P<0.05), whereas Penh values, IL-1β, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were increased (P<0.05). No significant differences were noted in these indices between the high dose iris xanthin group and the dexamethasone group (P>0.05). CONCLUSIONS: Iris xanthin can effectively alleviates airway inflammation and inhibits airway remodeling in asthmatic young mice, possibly through the suppression of the HMGB1/TLR4/NF-κB pathway. 目的: 探究鸢尾黄素对哮喘幼鼠气道炎症、气道重塑及高迁移率族蛋白B1（high mobility group box 1 protein, HMGB1）/Toll样受体4（Toll-like receptor 4, TLR4）/核因子κB（nuclear factor-κB, NF-κB）通路的影响。方法: 将60只雄性BALB/c幼鼠随机分为空白组、模型组、地塞米松组，以及鸢尾黄素低、中、高剂量组，每组10只。采用腹腔注射致敏剂［卵清蛋白（ovalbumin, OVA）20 μg+氢氧化铝凝胶2 mg］+4% OVA雾化吸入激发建立幼鼠哮喘模型。肺功能检测仪检测幼鼠肺容积（lung volume, LV）、每分钟静息通气量（resting ventilation per minute, VE）及气道反应性（Penh值）；苏木精-伊红染色观察并分析气道重塑情况；ELISA法检测肺泡灌洗液中白介素（interleukin, IL）-1β、IL-6、肿瘤坏死因子α（tumor necrosis factor alpha, TNF-α）含量；实时定量逆转录聚合酶链反应及Western blot法检测肺组织中HMGB1/TLR4/NF-κB通路相关mRNA及蛋白表达。结果: 与模型组比较，地塞米松组及鸢尾黄素低、中、高剂量组LV、VE均显著升高（P<0.05），其中鸢尾黄素各剂量组随剂量增加LV、VE升高（P<0.05）；地塞米松组及鸢尾黄素低、中、高剂量组Penh值、IL-1β、IL-6、TNF-α、气道重塑指标，以及HMGB1、TLR4、NF-κB p65 mRNA和HMGB1、TLR4、p-NF-κB p65蛋白表达水平均降低（P<0.05），其中鸢尾黄素各剂量组随剂量增加上述指标降低（P<0.05）。与地塞米松组比较，鸢尾黄素低、中剂量组LV、VE均降低（P<0.05），Penh值、IL-1β、IL-6、TNF-α、气道重塑指标，以及HMGB1、TLR4、NF-κB p65 mRNA和HMGB1、TLR4、p-NF-κB p65蛋白表达水平均升高（P<0.05）；鸢尾黄素高剂量组上述指标与地塞米松组比较差异无统计学意义（P>0.05）。结论: 鸢尾黄素能有效减轻哮喘幼鼠气道炎症，抑制气道重塑，可能与抑制HMGB1/TLR4/NF-κB通路有关。.

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