Improvement of hamster-lung fibrosis model by repeated intratracheal administration of bleomycin.

Suitable conditions of bleomycin (BLM)-treatment to effectively induce pulmonary fibrosis without high mortality were investigated in Syrian golden hamsters. Male 6-week-old hamsters were divided into 5 groups, each consisting of 5 animals. Groups 1-4 were intratracheally instilled with 2.5U/kg of BLM on day O and then repeatedly given BLM as follows: group 1, 2.5U/kg intratracheally on day 14; group 2, 1.0U/kg intratracheally on day 14; group 3, 1.0U/kg intratracheally each on days 7 and 14; group 4, 20U/kg intraperitoneally each on days 10and 14. Group 5 served as a vehicle control. The survival rate was 4/5 (80%) in groups l and 3, and 5/5 (100%) in other groups. One animal each in groups I and 3 was found dead on day 22, of which lungs histopathologically showed evident fibrosis accompanied with congestion, edema, inflammatory cell infiltration, and hemorrhage. The lung weight at the termination of the experiment on day 28 was the highest in group 1, and significantly higher in groups 1 (p<0.01) and 2 (p<0.05) than in group 5, well correlating with the histopathological severity of lungfibrosis. The lung weight of group 3 was also higher as compared to the group 5 value although this was not statistically significant and the lung weight of group 4 was almost comparable to that of group 5, again being in line with the histopathology of the lung. The results in the present study thus suggest that the repeated intratracheal instillation with 2.5U/kg BLM at intervals of 2 weeks may offer a favorable condition to induce diffuse lung fibrosis in hamsters.