抑郁对哮喘模型小鼠气道炎症及气道高反应性的影响

Effects of depression on airway inflammation and hyperresponsiveness in asthmatic mice

目的探讨抑郁对哮喘小鼠气道炎症及气道高反应性的影响。方法采用随机数字表法将40只Balb/c雄性小鼠分为正常组、单纯哮喘组、哮喘伴抑郁组和地塞米松组4组,每组10只。正常组采用0.9%氯化钠溶液雾化吸入;单纯哮喘组采用卵蛋白致敏与激发制备单纯哮喘模型;哮喘伴抑郁组和地塞米松组则在哮喘模型基础上给予4周未预知的慢性应激刺激;地塞米松组从给予慢性应急刺激开始起采用地塞米松0.5 mg/kg,1次/d,干预4周,其余各组采用0.9%氯化钠溶液。采用旷场试验分析小鼠行为学变化;采用强迫游泳试验分析小鼠抑郁水平;无创肺功能仪检测气道高反应性;ELISA法测定肺泡灌洗液IL-4、IL-5、IL-13水平及血清IgE水平;肺组织HE染色评价观察小鼠肺组织气道炎症。结果与单纯哮喘组比较,哮喘伴抑郁组小鼠中央活动时间和中央运动距离/总的活动距离比均明显减少,强迫游泳试验不动时间延长,小鼠增强呼气间歇值明显升高,肺泡灌洗液IL-5水平升高,肺组织气道炎症评分升高,差异均有统计学意义(均P<0.05)。结论抑郁可明显加重哮喘小鼠气道炎症及气道高反应性。

Objective To investigate the effects of depression on airway inflammation and airway hyperreactivity in asthmatic mice.Methods Forty Balb/c male mice were randomly divided into four groups:normal control group,asthma group,asthma with depression group,and dexamethasone group,with 10 mice in each group.Asthma model was induced by OVA protein sensitization and challenge,whereas asthma model with depression was prepared by unpredictable chronic mild stress plus with OVA sensitization and challenge.The normal control group was challenged with normal saline.The dexamethasone group was treated with dexamethasone,whereas other groups were treated with normal saline.Animal behavioral changes were assessed by the open field video tracking system.The depression level of mice was analyzed by forced swimming test.Airway reactivity was measured by Buxco's non-invasive system.The levels of IL-4,IL-5,IL-13 in broncho-alveolar lavage fluid(BALF)and serum IgE were determined by ELISA.Lung tissues were examined for inflammatory cell infiltration by HE staining.Results Compared with the asthma group,chronic mild stress significantly reduced the time and distance of the mice activities in the center field in the open field test,prolonged immobile time during forced swimming test,enhanced airway hyperresponsiveness to methacholine which was manifested by increased Penh value and elevated levels of IL-5 cytokine in the BALF,and markedly increased pathological airway inflammation score in lung tissues.Conclusion Depression can significantly increase airway inflammation and hyperresponsiveness in asthmatic mice.