The Establishment of an Animal Model of Pulmonary Fibrosis

摘要

An animal model of interstitial pulmonary fibrosis has been developed in the hamster by a single endotracheal instillation of bleomycin. Edema, mild hemorrhage, and an outpouring of polymorphonuclear neutrophils are followed by an infiltration by macrophages and lymphocytes, the latter persisting for up to 18 months. Interstitial thickening and hyperplasia and metaplasia of type II epithelial cells become evident within a few days. Broad bands and sheets of collagen are observable by 30 days. The overall process reaches a peak of severity at about 30 days, shows mild improvement by 60 days, more striking improvement by 90 days, and much slower resolution subsequently. Physiologically there is diminution in total lung capacity, quasi-static compliance, vital capacity, and diffusing capacity for carbon monoxide. Arterial blood gas measurements in awake animals have shown hypoxemia without hypercapnia. Biochemical measurements have shown an increase of DNA in the lungs of about 25% over control by the 8th day which return to normal by the 90th day. Whole lung collagen and elastin were normal at 8 days, increased by about 50% over control at 30 days, approximately doubled by 60 days, and remain quite markedly elevated at the final observation point of 90 days. Penicillamine results in a diminution in the collagen content of the lungs of animals with bleomycin induced interstitial pulmonary fibrosis but does not give rise to a significant change in the mechanical properties of the lungs. The hysteresis ratio in bleomycin induced lung fibrosis is almost twice that in normals.