白介素-1受体拮抗剂对致敏豚鼠的抗喘作用

目的 :观察白介素 1受体拮抗剂 (IL 1ra)对致敏豚鼠的抗喘作用。方法 :用卵白蛋白致敏豚鼠 ,用张力换能器和MedLab软件记录气道平滑肌的肌张力和收缩活动。结果 :整体实验时 ,在 0 .3 3～9.0mg·kg- 1 剂量范围内 ,IL 1ra能使组胺 乙酰胆碱及卵白蛋白诱发的致敏豚鼠哮喘的潜伏期延长 ,动物跌倒率降低。此作用具有剂量依赖性。其中 ,9.0mg·kg- 1 剂量组的作用与异丙基肾上腺素相同 ;离体实验时 ,3× 1 0 - 7mol·L- 1 以上浓度的IL 1ra对气管平滑肌具有直接松弛作用 ,其EC50 为 5 .88×1 0 - 7mol·L- 1 ;1 0 - 7mol·L- 1 的IL 1ra能对抗卵白蛋白引起的气管平滑肌肌张力的增加 ;3×1 0 - 7mol·L- 1 以上剂量组的IL 1ra预防给药则能使卵白蛋白诱发的气管平滑肌的收缩程度显著降低 ,其IC50 为 4.48× 1 0 - 7mol·L- 1 。结论 :IL 1ra能直接松弛致敏豚鼠的气管平滑肌 ,拮抗多种抗原诱发的致敏豚鼠的哮喘发作。

Anti-asthmatic effects of interleukin-1 receptor antagonist in sensitized guinea pigs

AIM: To observe the anti-asthmatic ef-fects of interleukin-1 receptor antagonist (IL-1ra) in sen-sitized guinea pigs. METHODS: Sensitized guinea pigswere made by ovalbumin, and the tension and contractionof tracheal smooth muscles were measured by force-dis-placement transducer and MedLab software. RESULTS:In the doses of 0.33 - 9.0 mg@ kg- 1, IL- 1 ra prolongedthe asthmatic incubation period and reduced animal tum-ble ratio in asthma guinea pigs induced by histamine-ace-tylcholine or ovalbumin. These effects were dose-depen-dent. In vitro, IL-1 ra could directly relax tracheal smoothmuscles up the dose of 3 × 10-7mol@L-1 and the EC50value was 5.88 × 10-7mol@L-1. IL-1ra antagonized theincrease of trachea tension stimulated by ovalbumin at thedose of 10-7mol@ L-1. Moreover, IL - 1ra prevented tra-cheal smooth muscle contraction induced by ovalbumin upthe dose of 3 × 10-7 mol@L-1, and the IC50 value was4.48 × 10-7mol@L-1. CONCLUSIONS: IL-1ra can di-rectly relax tracheal smooth muscles in sensitized guineapigs, and antagonize asthma caused by many kinds of antigens.