The Dynamic Evolution And Differentiation Of Bleomycin-induced Pulmonary Fibrosis In Mice

Objective:To discuss the best methods and dose of bleomycin to induce the pulmonary fibrosis.Method:One hundred and twenty six8-week old male ICR mice were randomly divided into singular-large-dose (OLD) and multiple-low-dose (MLD) model groups. The OLD model was classified into four subgroups with BLM injection in a dose of200mg/(kg·bw),150mg/(kg·bw),100mg/(kg·bw) and negative control (saline10ml/(kg·bw)), and six mice were sacrificed at7,14and21days after injection, respectively. The multiple low dose models were classified into10mg/(kg·bw)/d group BLM injection once per day for consecutive14days, and negative control group. Six mice were killed at14,21and28days after BLM and saline injection, respectively. The body weight, survival rate, pathological changes and amount of type III collagen in the lung tissue were observed.Results:①In the OLD models, the scores of pulmonary alveolitis and fibrosis of the mice in all groups were significantly higher than that of the normal group (P<0.05), except the100mg/(kg·bw) BLM and150mg/(kg·bw) BLM groups (P>0.05) sacrificed at7days. The expressions of type III collagen in all groups were significantly higher than that of the normal group (P<0.05) except the100mg/(kg·bw) BLM group (P>0.05) killed at7days. The expression of type III collagen in each group at21days reached a peak, and the200mg/(kg·bw) group killed at21days was the highest. The mortality rate was0.②In the MLD models, compared with the normal group, the pulmonary alveolitis and fibrosis of all the groups were significantly higher than that in the control group (P<0.05), progressively increasing with time, and peaked at28days. Eleven MLD model mice died and the mortality rate was30.56%.Conclusion:The results of our study demonstrate that the mouse models developed at21days after the BLM200mg/(kg·bw) injection is the most successful, with advantages such as low mortality, simple operation, effective, good safety and convenience in use. Therefore it may become an ideal method in establishing animal model of pulmonary fibrosis.