Nabe T, Shinoda N, Yamada M, Sekioka T, Saeki Y, Yamamura H, Kohno S
Department of Pharmacology, Kyoto Pharmaceutical University, Japan.
Jpn J Pharmacol. 1997 Sep;75(1):65-75. doi: 10.1254/jjp.75.65.
To develop a model of chronic experimental asthma in guinea pigs, the animal was forced to inhale the mist of a low dose of ovalbumin (OA) adsorbed on fine Al(OH)3 for sensitization once every 4 weeks. The animal was challenged by inhalation with the mist of OA on day 14 after the respective sensitizations. Either the first or the second antigen challenge markedly induced an early asthmatic response (EAR), whereas there was hardly any late asthmatic response (LAR). At the 3rd challenge, LAR also emerged with some severity. These dual responses were consistently observed until the 10th challenge. On the other hand, repeated inhalation/challenge, once every 2 weeks, with OA alone at the same dose tended to lead to the desensitization of the EAR. In addition, LAR was hardly observed throughout the experiments. In both groups, gamma 1 and IgE levels in the serum were elevated by the repetitive antigen inhalations, yet no obvious relationship between these antibody levels and the intensity of either EAR or LAR was recognized. The present results indicate that the asthmatic model with reproducible EAR and LAR developed in this study appears to be very beneficial for the investigation of bronchial asthma and for the assessment of anti-asthma drugs.
为建立豚鼠慢性实验性哮喘模型,每隔4周让动物吸入吸附于精细氢氧化铝上的低剂量卵清蛋白(OA)雾剂进行致敏。在每次致敏后第14天,通过吸入OA雾剂对动物进行激发。第一次或第二次抗原激发均显著诱导早期哮喘反应(EAR),而几乎没有迟发性哮喘反应(LAR)。在第三次激发时,LAR也出现且有一定严重程度。这些双重反应一直持续到第十次激发。另一方面,以相同剂量单独使用OA每2周重复吸入/激发往往会导致EAR脱敏。此外,在整个实验过程中几乎未观察到LAR。在两组中,重复吸入抗原均使血清中γ1和IgE水平升高,但未发现这些抗体水平与EAR或LAR强度之间存在明显关系。本研究结果表明,本研究中建立的具有可重复性EAR和LAR的哮喘模型似乎对支气管哮喘的研究及抗哮喘药物的评估非常有益。