磷酸二酯酶3抑制剂减轻致敏豚鼠模型的咳嗽反应(英文)

Phosphodiesterase 3 inhibitor attenuates cough response in a sensitized guinea pig model

目的:研究选择性磷酸二酯酶3抑制剂奥普力农对卵蛋白致敏和激发豚鼠咳嗽反应的影响。方法:卵蛋白致敏豚鼠40只,随机分成对照组、激发组、奥普力农组和氨茶碱组,每组10只。1%卵蛋白或生理盐水雾化吸入激发后2 h,腹腔内分别注射生理盐水、25mg/kg的奥普力农或氨茶碱。激发后24h,奥普力农组和氨茶碱组豚鼠腹腔依次注射2.5mg/kg和25mg/kg的奥普力农或氨茶碱,测量吸入辣椒素溶液诱导的咳嗽反应和对乙酰甲胆碱溶液的气道反应性(PC150),分析支气管肺泡灌洗液中的细胞数和细胞成分。结果:对照组和激发组豚鼠的咳嗽频率分别为(5±1)times/3 min和(24±3)times/3 min(P<0.05),PC150分别为(659±57)mg/L和(238±67)mg/L(P<0.05)。25mg/kg的奥普力农能明显抑制这些改变,咳嗽频率和PC150分别为(15±2)times/3min和(580±45)mg/L (P<0.05),作用强于同剂量氨茶碱的(18±2)times/3min和(438±52)mg/L(P<0.05)。而奥普力农组豚鼠支气管肺泡灌洗液中细胞总数和嗜酸粒细胞比例和激发组比较无显著差异(P>0.05)。结论:选择性磷酸二酯酶3抑制剂通过支气管舒张作用减轻嗜酸粒细胞性气道炎症所致咳嗽。

AIM： To investigate the effects of selective phosphodiesterase 3 inhibitor olprinone on cough response in guinea pigs sensitized and challenged with ovalbumin. METHODS： Forty sensitized guinea pigs were randomly divided into control （ n = 10）, challenged （ n = 10）, olprinone （ n = 10） and aminophylline group （ n = 10 ）. Two hours after challenged with the aerosol of 1% ovalbumin or saline, animals were intraperitoneally injected either with saline,25 mg/kg of olprinone or 25 mg/kg aminophylline. At 24 h, the injection was repeated with 2. 5 mg/kg and 25 mg/kg olprinone or 2. 5 mg/kg and 25 mg/kg aminophylline respectively in olprinone and aminophylline group, cough response to inhaled capsaicin and airway responsiveness to methacholine （PC150） were measured. Then, total cell number and differential counts were analyzed in bronchoalveolar lavage fluid. RESULTS： The cough frequency was （5 ± 2） times/3 min in control group and （24 ± 3 ） times/3 min in challenged group （ P 〈 0. 05 ）, while PC150 was （659 ＋ 57 ） mg/L in control group and （238 ＋ 67 ） mg/L inchallenged group （ P 〈 0. 05 ）. 25 mg/kg olprinone significantly inhibited the augmented cough response and airway hyperresponsiveness, the cough frequency and PC150 were （15 ±2） times/3 min and （580 ±45） mg/L （P 〈 0. 05 ）, which differed significantly from （18 ± 2） times/3 min and （438± 52） mg/L in aminophilline group （P 〈 0. 05）. However, olprinone failed to reverse the elevated total cell number and percentage of eosinophils in bronchoalveolar lavage fluid from guinea pigs challenged with ovalbumin （P 〉 0. 05 ）. CONCLUSION： Phosphodiesterase 3 inhibitor attenuates cough response associated with eosinophilic airway inflammation by bronchodilatory effect.