白细胞介素1受体拮抗剂对豚鼠哮喘的作用

EFFECTS OF RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST ON EXPERIMENTAL ASTHMA IN GUINEA-PIGS

从整体角度研究白介素1受体拮抗剂(IL-1ra)的抗哮喘作用及对豚鼠离体气管平滑肌活动的影响。结果表明:整体状态下,IL-1ra用量为0.25～4.0mg·kg^(-1)时,能剂量依赖性地延长组织防-乙酰胆碱(His-Ach)诱发的豚鼠哮喘潜伏期,降低动物跌倒率;离体试验时,IL-1ra浓度高于10^(-9)mol·L^(-1)对气管平滑肌具有直接松弛作用,EC_(50)为8.06×10^(-3)mol·L^(-1);当浓度高于10^(-7)mol·L^(-1)时,能对抗His、Ach及5-羟色胺(5-HT)引起气管平滑肌肌张力增加;当浓度为10^(-7)～10^(-3)mol·L^(-1)时,预防给药能抑制His诱发气管平滑肌收缩,最大收缩效应降低,并可对抗Ach及5-HT对气管平滑肌的兴奋作用,但当其浓度低于10^(-6)mol·L^(-1)时,效应相反。

The anti-effects of interleukin-1 receptor antagonist (IL-lra) on asthma and isolated guinea-pig trachea smooth muscle contraction in vivo and in vitro was described. The results showed that in the dose of 0. 25 - 4. 0 mg · kg-1, IL-lra could prolong the asthmatic incubation period , and reduce animal tumble ratio in asthmatic guinea-pig induced by histamine-acetylcholine. These effects were dose-dependent. In vitro > IL-lra could directly relax trachea smooth muscles at the dose of 10-9 mol · L-1, its EC50 value was 8. 06×10-8mol · L-1, and it could antagonize the increase of trachea tension stimulated by His, Ach and 5-hydroxytryptamine (5-HT) above the dose of 10-7 mol · L-1. IL-lra could also prevent contraction of trachea smooth muscles induced by His at the dose of 10-7 - 10-8 mol · L-1, its maximal effects decreased. Moreover IL-lra could antagonize trachea smooth muscles excitation induced by Ach or 5-HT between 10-7-10-3mol · L-1, but it might have the reverse effects under the dose of 10-9 mol · L-1.