用离体兔气管平滑肌建立抗鼻病毒药物的药效学评价模型

Establishment of isolated rabbit airway smooth muscles responsiveness model for the pharmacodynamic study of anti-rhinoviruses drugs

人鼻病毒(human rhinovirus,HRV)是引起病毒性呼吸道感染的最常见病原体,目前尚无有效治疗药物。由于HRVs绝大多数血清型仅对灵长类动物易感,对常用实验动物不感染,目前多在细胞水平对抗HRVs药物进行筛选与评价,这对抗HRVs药物的有效性研究明显不足。本文根据HRVs对呼吸道感染的特点,以离体气管平滑肌(ASM)收缩反应变化为评价指标,建立了可模拟呼吸症状的筛选模型,在此模型上接种鼻病毒后ASM对于激动剂引发的收缩反应显著增强150%,舒张反应明显减弱至63%,而预先加入已经过细胞初筛有效的化合物后,可显著改善鼻病毒引发的收缩反应异常,表明所建立的评价模型可用于抗鼻病毒药物的进一步筛选。

Human rhinoviruses （HRVs） are the causative pathogens in more than half of viral upper respiratory tract infections. Currently,no antiviral agents that are active against HRVs are available for clinical use. Because only higher primates are susceptible to HRVs,the screening of new drug is most commonly based on the cell line model. In this study,isolated rabbit airway smooth muscles （ASM） tissue model has been established,and the airway responsiveness with different treatment has been examined. Relative to control tissues,the maximal constrictor （Tmax） response to ACh increased significantly 150% in ASM inoculated with HRV,and relaxation to isoproterenol has been attenuated to 63%. And the abnormal responsiveness can be inhibited in presence of pretreatment with several new compounds which have been exhibited effective anti-HRV activity on cell lines. The results demonstrate that the established ASM model will be applied to screening the anti-HRVs drugs.