氯喹对哮喘小鼠气道高反应性的抑制作用

Inhibitory effect of chloroquine on airway hyperresponsiveness in asthmatic mice

目的探讨氯喹对哮喘小鼠气道高反应性的作用及其可能机制。方法 Balb/c小鼠随机分为对照组、哮喘组、氯喹治疗组、地塞米松治疗组、氯喹+地塞米松治疗组,除对照组外,其余各组小鼠均给予OVA致敏和激发,建立哮喘小鼠模型,于每次激发前腹腔注射给药,对照组则于同一时间予等量PBS处理,末次激发后24 h内小鼠肺功能仪检测小鼠气道高反应性;检测支气管肺泡灌洗液(BALF)中细胞总数及分类计数;制作肺组织病理切片,HE染色后光镜下观察病理变化;ELISA检测支气管肺泡灌洗液中细胞因子IL-6、PGF2α水平。结果氯喹可明显降低哮喘小鼠气道高反应性(吸入25 mg/ml Ach时4.5±0.4 vs 6.1±0.9,P<0.05,吸入50 mg/ml Ach时4.6±0.5 vs 8.2±1.0,P<0.001);明显降低哮喘小鼠支气管肺泡灌洗液中炎症细胞数(P<0.01);显著降低哮喘小鼠病理评分(P<0.05);可一定程度降低哮喘小鼠BALF中PGF2α因子水平;与地塞米松合用可明显减轻哮喘小鼠支气管细支气管周围炎症(P<0.05)、血管周围炎症(P<0.01)、肺组织病理评分(P<0.001),明显降低哮喘小鼠BALF中IL-6因子水平(P<0.05)。结论氯喹可抑制哮喘小鼠气道高反应性;地塞米松与氯喹合用较单独用药效果更好,可能对中性粒细胞参与的哮喘有效。

Objective To investigate the effect of chloroquine on airway hyperresponsiveness in asthmatic mice and explore the possible mechanism. Methods Balb/c mouse models of asthma established using OVA received intraperitoneal injections of chloroquine, dexamethasone, or both prior to OVA challenge. Within 24 h after the final challenge, airway hyperresponsiveness（AHR） of the mice was assessed, and the total cell count and the counts of different cell populations in the bronchoalveolar lavage fluid（BALF） were determined under light microscopy. The severity of lung inflammation was evaluated using HE staining, and the concentrations of IL- 6 and PGF2αin the BALF were detected by enzyme- linked immunosorbent assay（ELISA）. Results Chloroquine pretreatment significantly decreased AHR（P〈0.001） in the asthmatic mice and reduced the total cell count（P〈0.01）, eosinophils（P〈0.001）, neutrophils（P〈0.01）, and PGF2αlevels in the BALF.Chloroquine combined with low- dose dexamethasone significantly lessened inflammations around the bronchioles（P〈0.05）and blood vessels（P〈0.01） in the lung tissue, and obviously lowered IL- 6（P〈0.05） and PGF2α（P〈0.001） in the BALF in the asthmatic mice. Conclusion Chloroquine can inhibit AHR in asthmatic mice and produce better anti-inflammatory effect when combined with dexamethasone for treatment of neutrophilic asthma.