目的 探讨内皮素受体拮抗剂对过度通气诱导豚鼠支气管痉挛的影响.方法 ①将19只小鼠分成两组.(A)bosentan组:在过度通气前予bosentan;(B)对照组:在过度通气前给予生理盐水.在诱发前后分别测定肺阻力与肺顺应性,用含5%CO2、95%O2干燥混合气通过动物呼吸机提供机械通气.分别收集肺泡灌洗液.②14例哮喘病人和141例健康对照者,用脉冲振荡仪测定呼吸阻抗,而后进行运动激发试验并再次测定呼吸阻抗.最后,收集两组血清并测定ET-1浓度.结果 ①动物试验组,过度通气显著诱发对照组肺阻力增加,为3.28倍,肺顺应性下降,下降为49.9%,而bosentan组无明显变化.肺泡灌洗液bosentan组明显多于对照组(P<0.001).②临床试验组哮喘病人在运动后5～10min外周阻力大于中央阻力,诱发前后,R5-R20,Zrespir,resonance frequency(Fres)and X5均有显著变化(Table6、Fig3).R5-R20增高≥0.032kPa/L/s,71.4%哮喘病人X5的变化率≥41%,571%病人VT-Zrespir-图表现气流诱捕.哮喘组血浆内皮素-1浓度为(66.6±12.13)ng/mL,对照组为(40.7±5.6)ng/mL(P=0.022),哮喘组运动激发前后呼吸阻抗和血浆内皮素-1浓度有明显相关性.结论 实验证明内皮素受体拮抗剂能抑制过度通气诱发豚鼠支气管收缩.运动性周围支气管痉挛中ET1起重要作用.%Objective To investigate the effect of endothelin on mechanism of exercise-induced bronchoconstriction.Methods 1) In animal experiment 19 pathogen-free Hartley guinea pigs were divided into 2 groups randomly.(A) Bosentan group: bosentan were administered prior to isocapnic hyperpnea challenge; (B) Control group: the control group was given 0.9% NaCI at same condition.Lung resistance (RL) and dynamic compliance (Cdyn) of 2 groups were measured before isocapnic hyperpnea challenge,the ventilator were provided by animal breathing machine using dry mixture gas contained 5%CO2,95%O2,volume of bronchial alveolar lavage fluid (BALF) was collected.2) In clinical experiment asthmatics (n=14)and healthy subjects (n=14) took part in the experiment.Respiratory impedance was measured with IOS.Exercise challenge with an ergometer.After the challenge,measurement with IOS was made immediately again.After IOS measurement,the blood samples from both groups for ET-1 concentration were taken.decrease in Cdyn(49.9%) in the control group.In bosentan group,RL and Cdyn did not change significantly.clinical experiment the maximal increase of respiratory impedance occurred at 5min-10min after exercise and the increment magnitude of peripheral resistance was more than that of central resistance in asthmatics.After challenge,R5,R5-R20,Zrespir and X5 from patients changed significantly in patients.The increment change value of R5-R20 from all asthmatics≥0.032kPa/L/s).The change ratio of X5 from 71.4% asthmatics≥41%.Air trapping was expressed in VT-Zrespir graph in 57.1% patients.The serum concentration of ET-1 from asthmatics was (66.6±12.1) ng/mL,which of control group was (40.7±5.6) ng/mL (P=0.022).In asthmatics,there is a significant correlation between the change value of airway resistance and the serum concentration of ET-1.Conclusion Endothelin receptor antagonist bosentan can restrain bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs.The endothelin-1 may be an important factor in the pathogenesis of the peripheral bronchoconstriction elicited by exercise challenge.
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