CAJ | 학술논문

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。
목적：탐토록규대효천소서기도고반응성적작용급기가능궤제。방법 Balb/c소서수궤분위대조조、효천조、록규치료조、지새미송치료조、록규+지새미송치료조，제대조조외，기여각조소서균급여OVA치민화격발，건립효천소서모형，우매차격발전복강주사급약，대조조칙우동일시간여등량PBS처리，말차격발후24 h내소서폐공능의검측소서기도고반응성；검측지기관폐포관세액（BALF）중세포총수급분류계수；제작폐조직병리절편，HE염색후광경하관찰병리변화；ELISA검측지기관폐포관세액중세포인자IL-6、PGF2α수평。결과록규가명현강저효천소서기도고반응성（흡입25 mg/ml Ach시4.5±0.4 vs 6.1±0.9，P<0.05，흡입50 mg/ml Ach시4.6±0.5 vs 8.2±1.0，P<0.001）；명현강저효천소서지기관폐포관세액중염증세포수（P<0.01）；현저강저효천소서병리평분（P<0.05）；가일정정도강저효천소서BALF중PGF2α인자수평；여지새미송합용가명현감경효천소서지기관세지기관주위염증（P<0.05）、혈관주위염증（P<0.01）、폐조직병리평분（P<0.001），명현강저효천소서BALF중IL-6인자수평（P<0.05）。결론록규가억제효천소서기도고반응성；지새미송여록규합용교단독용약효과경호，가능대중성립세포삼여적효천유효。
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 hyper-responsiveness (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 PGF2α in 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 PGF2α levels 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.