Assistant Lecturer, 'Gr T Popa' University of Medicine and Pharmacy Iaşi, Pulmonary Disease University Hospital, Department of Internal Medicine-Pulmonary Disease, 30 Dr I Cihac Street, 700115 Iasi, Romania.
Expert Opin Drug Discov. 2009 Sep;4(9):939-46. doi: 10.1517/17460440903186100.
Idiopathic pulmonary fibrosis (IPF) is a disease with high morbidity and mortality for which current medications are not effective. Therefore, identification of potential therapies is of paramount importance. The preclinical evaluation of novel compounds in animal models represents a critical step in drug development.
To describe features and limitations of common animal models of pulmonary fibrosis and discuss relevant preclinical and clinical data on novel potential IPF therapies.
Review of the existing literature on such models with a special focus on the bleomycin model and its usefulness for the IPF preclinical drug testing.
The model of bleomycin-induced pulmonary fibrosis has the advantages of being well established, reproducible and both time- and cost-efficient. However, it has major limitations as it only mimics some features of human IPF. Most importantly, it is initiated by acute lung injury and is at least partially reversible, which is strikingly different from IPF. The failure in establishing effective IPF therapies despite strong efforts in the last decade is partly attributable to our uncritical trust in the models of lung fibrosis and the false belief that they truly reflect what is going on in human disease.
特发性肺纤维化（IPF）是一种发病率和死亡率都很高的疾病，目前的药物对此并不有效。因此，寻找潜在的治疗方法至关重要。在动物模型中对新型化合物进行临床前评估是药物开发的关键步骤。
描述常见的肺纤维化动物模型的特点和局限性，并讨论新型潜在 IPF 治疗方法的相关临床前和临床数据。
对这类模型的现有文献进行综述，特别关注博来霉素模型及其在 IPF 临床前药物测试中的应用。
博来霉素诱导的肺纤维化模型具有建立良好、可重复、省时、省钱的优点。然而，它也有很大的局限性，因为它仅模拟了人类 IPF 的一些特征。最重要的是，它是由急性肺损伤引起的，至少部分是可逆转的，这与 IPF 有很大的不同。尽管在过去十年中进行了大量努力，但仍未能开发出有效的 IPF 治疗方法，部分原因是我们对肺纤维化模型的盲目信任，以及对这些模型能真实反映人类疾病的错误信念。
