基础医学与临床 ›› 2023, Vol. 43 ›› Issue (3): 402-407.doi: 10.16352/j.issn.1001-6325.2023.03.402

• 研究论文 • 上一篇    下一篇

地塞米松减轻过敏性哮喘模型小鼠气道炎性反应

刘芬, 胡润芳, 茅松, 徐敏, 石文静, 陈凌*   

  1. 上海交通大学附属第六人民医院 儿科,上海 200233
  • 收稿日期:2022-02-28 修回日期:2022-05-25 出版日期:2023-03-05 发布日期:2023-02-27
  • 通讯作者: * candice131@sjtu.edu.cn
  • 基金资助:
    上海市自然科学基金(19ZR1438400)

Dexamethasone attenuates airway inflammation in mouse models with allergic asthma

LIU Fen, HU Runfang, MAO Song, XU Min, SHI Wenjing, CHEN Ling*   

  1. Department of Pediatrics, the Affiliated Sixth People's Hospital of Shanghai Jiao Tong University, Shanghai 200233, China
  • Received:2022-02-28 Revised:2022-05-25 Online:2023-03-05 Published:2023-02-27
  • Contact: * candice131@sjtu.edu.cn

摘要: 目的 观察地塞米松(DEX)对过敏性哮喘模型小鼠气道炎性的影响并探讨相关机制。方法 将小鼠随机分为对照组、哮喘组、地塞米松组。哮喘组小鼠于实验第0、7、14天皮下注射卵清蛋白(OVA)/氢氧化铝混合液,第21、22天1% OVA混悬液雾化吸入20 min;地塞米松组在哮喘组基础上于每次雾化吸入前3 h地塞米松(2 mg/kg)腹腔注射。末次雾化结束测定小鼠气道阻力,24 h后收集肺泡灌洗液(BALF),Wright-Giemsa染色后行细胞分类计数;ELISA测定BALF中IL-6、IL-18和IL-1β等浓度;免疫组织化学法(IHC)检测肺组织NLRP3、IL-1β蛋白表达,HE染色观察肺组织病理。结果 与对照组比较,哮喘组小鼠气道高反应性(AHR)明显增高;BALF中嗜酸性粒细胞、中性粒细胞等炎性细胞数量明显增加;IL-5、IL-6、IL-18和IL-1β表达均升高(P<0.01);肺组织NLRP3、IL-1β蛋白表达增强。与哮喘组比较,地塞米松组小鼠AHR显著降低,BALF中炎性细胞总数、嗜酸性粒细胞、中性粒细胞均明显减少(P<0.01),IL-5、IL-6、IL-18和IL-1β表达水平显著降低(P<0.01);肺组织NLRP3、IL-1β蛋白表达降低;肺组织HE染色结果显示地塞米松组小鼠肺组织炎性细胞浸润明显减轻,炎性指数显著降低(P<0.01)。结论 地塞米松抑制OVA诱导的NLRP3炎性小体活化及IL-5、IL-6、IL-18等炎性因子分泌,降低气道高反应性,有效缓解过敏性哮喘小鼠气道炎性反应。

关键词: 支气管哮喘, NLRP3, IL-1β, 地塞米松, 气道炎性反应

Abstract: Objective To observe the inhibitory effect and the relative mechanisms of dexamethasone(DEX) on airway inflammation in mouse models with allergic asthma. Methods BALB/c mice were randomly divided into control group, asthma group, and dexamethasone group. The mice in the asthma group were subcutaneously injected with ovalbumin (OVA)/aluminum hydroxide mixture on day 0, 7, 14 and nebulized with 1% OVA suspension for 20 minutes on day 21 and 22. The mice in the dexamethasone group were given intraperitoneal injection of dexamethasone 3 hours before each inhalation based on the asthma group. The airway resistance of mice was measured at the end of the last aerosol inhalation, the cells in bronchoalveolar lavage fluid (BALF) were counted by Wright-Giemsa staining. The concentration of inflammatory factors in BALF was measured by ELISA. The protein expression of NLRP3 and IL-1β were detected by immunohistochemistry (IHC), and lung histopathological analysis was performed. Results Compared with the control group, the airway hyperresponsiveness (AHR) of mice in the asthma group was significantly enhanced; The numbers of eosinophils and neutrophils in BALF were significantly increased (P<0.01); IL-5, IL-6, IL-18 and IL-1β expression in BALF were significantly increased (P<0.01); The expression of NLRP3 and IL-1β in lung tissue was enhanced as shown by IHC result. Compared with the asthma group, AHR of mice in the dexamethasone group was significantly reduced; The expression levels of IL-18 and IL-1β were also significantly decreased(P<0.01); The protein expressions of NLRP3 and IL-1β in the lung tissue were decreased; The pathological histology analysis showed inflammatory infiltration in lung tissue from the dexamethasone group was significantly reduced (P<0.01). Conclusions Dexamethasone suppresses NLRP3 inflammasome activation induced by OVA, decreases inflammatory factors expression and airway hyperresponsiveness, thereby effectively alleviates the airway inflammation of asthmatic mice.

Key words: bronchial asthma, NLRP3, IL-1β, dexamethasone, airway inflammation

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