内皮素受体拮抗剂对豚鼠哮喘模型的影响

Effects of endothelin antagonist on bronchoconstriction elicited by isocapnic hyperpnea in Guinea pigs

目的 通过内皮素 (ET)受体非肽类拮抗剂Bosentan对豚鼠等CO2 过度通气模型影响的观察 ,探讨运动性哮喘的发病机制以及ET受体拮抗剂的治疗作用。方法 健康Hartley株豚鼠 19只分为两组。Bosen tan组 10只 ,按每次 30mg/kg腹腔注射 ,3次。对照组 9只 ,注射用水腹腔注射。先测定肺阻力和动态肺顺应性。应用微型人工呼吸机和干燥 5 %CO2 、95 %O2 气体进行等CO2 过度通气 ,设定呼吸频率 10 0次 /min ,潮气量 8ml,时间 5min。然后复查肺阻力和动态肺顺应性。结果 对照组过度通气后肺阻力显著增加 ,动态肺顺应性明显下降。Bosentan组过度通气后上述指标无明显改变。Bosentan组支气管肺泡灌洗液回收率明显高于对照组。结论 ET参与运动性哮喘发病机制。ET受体拮抗剂Bosentan抑制等CO2 过度通气所引起的豚鼠支气管痉挛 。

Objective To investigate the effects of endothelin antagonist, Bosentan on bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs and to explore the effect of endothelin in the pathogenesis of exercise induced asthma (E1A). Methods 19 pathogen free Hartley guinea pigs were divided into two groups. A)Bosentan group ( n =10), which was administered by intraperitoneal injection (30 mg/kg) in 24,16 and 8 h respectively before isocapnic hyperpnea challenge. B) Control group ( n =9), water was injected intraperitoneally(lml/kg) 24,16,and 8 h prior to the challenge. A rodent respirator with dry 5% CO 2, 95% O 2 mixture at room emperature provided mechanical ventilation (VT 8 ml/animal, 100 breaths/min) for 5 min. The lung resistance (RL) and the dynamic compliance (Cdyn) of the two groups were measured before and after isocapnic hyperpnea challenge. The percentages of BALF collected in both groups were assessed. Results In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in RL and decrease in Cdyn. RL and Cdyn of the guinea pigs from Bosentan group did not change significantly.The percentage of BALF collected in Bosentan group was more than that in the control group. Conclusion It was demonstrated that ET receptor antagonist Bosentan inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs. It is suggested that ET receptor antagonist might be beneficial in prevention and treatment of exercise induced asthma. The present investigative profile makes Bosentan a potentially useful drug in the management of clinical disorders associated with bronchoconstriction.