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[虹膜黄质对哮喘幼鼠气道炎症、气道重塑及HMGB1/TLR4/NF-κB通路的影响]

[Effects of iris xanthin on airway inflammation, airway remodeling, and the HMGB1/TLR4/NF-κB pathway in asthmatic young mice].

作者信息

Li Yue-Yun, Wang Xiao-Fang, Fu Yan, Wang Yan-Rui

机构信息

Department of Pediatrics, Xinxiang Central Hospital, Xinxiang, Henan 453000, China.

出版信息

Zhongguo Dang Dai Er Ke Za Zhi. 2024 Jun 15;26(6):639-645. doi: 10.7499/j.issn.1008-8830.2312023.

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 (<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 (<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 (<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 (<0.05). No significant differences were noted in these indices between the high dose iris xanthin group and the dexamethasone group (>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.

摘要

目的

探讨虹膜黄质对哮喘幼鼠气道炎症、气道重塑及高迁移率族蛋白B1(HMGB1)/Toll样受体4(TLR4)/核因子κB(NF-κB)通路的影响。

方法

将60只雄性BALB/c幼鼠随机分为6组:空白组、模型组、地塞米松组以及虹膜黄质低、中、高剂量组,每组10只。通过腹腔注射致敏剂[卵清蛋白(OVA)20μg+氢氧化铝凝胶2mg]诱导哮喘模型,随后吸入4%OVA气雾剂。使用肺功能测试仪测量肺功能,以确定肺容积(LV)、每分钟静息通气量(VE)和气道反应性(Penh值)。采用苏木精-伊红(HE)染色检查并分析气道重塑。使用酶联免疫吸附测定(ELISA)法定量支气管肺泡灌洗液中白细胞介素(IL)-1β、IL-6和肿瘤坏死因子α(TNF-α)的含量。采用实时荧光定量聚合酶链反应和蛋白质免疫印迹分析评估肺组织中HMGB1/TLR4/NF-κB通路相关mRNA和蛋白质的表达。

结果

与模型组相比,地塞米松组和虹膜黄质处理组(低、中、高剂量)的LV和VE显著增加(<0.05),虹膜黄质组呈剂量依赖性增加。此外,Penh值、IL-1β、IL-6、TNF-α和气道重塑指标,以及HMGB1、TLR4和NF-κB p65的mRNA水平和HMGB1、TLR4和p-NF-κB p65的蛋白质水平均呈剂量依赖性降低(<0.05)。与地塞米松组相比,虹膜黄质低、中剂量组的LV和VE降低(<0.05),而Penh值、IL-1β、IL-6、TNF-α和气道重塑指标,以及HMGB1、TLR4、NF-κB p65的mRNA水平和HMGB1、TLR4和p-NF-κB p65的蛋白质水平升高(<0.05)。虹膜黄质高剂量组与地塞米松组之间这些指标无显著差异(>0.05)。

结论

虹膜黄质可有效减轻哮喘幼鼠的气道炎症并抑制气道重塑,可能是通过抑制HMGB1/TLR4/NF-κB通路实现的。

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