Dynamic evolution and comparison of different dose-bleomycin-induced pulmonary fibrosis in mice

Objective To explore the optimal methods and dose of bleomycin to induce pulmonary fibrosis in mice.Methods One hundred and twenty six 8-week old male ICR mice were randomly divided into singule-large-dose(OLD) and multiple-low-dose(MLD) model groups.The OLD model was classified into four subgroups with BLM injection in a dose of 200 mg/(kg·bw),150 mg/(kg·bw),100 mg/(kg·bw) and negative control(saline 10 ml/(kg·bw)),and six mice were sacrificed at 7,14 and 21 days after injection,respectively.The multiple low-dose models were classified into 10 mg/(kg·bw)/d group BLM injection once per day for consecutive 14 days,and negative control group.Six mice were killed at 14,21 and 28 days 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 ① In 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 the 100 mg/(kg·bw)BLM and 150 mg/(kg·bw)BLM groups(P0.05) sacrificed at 7 days.The expressions of type Ⅲ collagen in all groups were significantly higher than that of the normal group(P0.05) except the 100 mg/(kg·bw)BLM group(P0.05) killed at 7 days.The expression of type Ⅲ collagen in each group at 21 days reached a peak,and the 200 mg/(kg·bw) group killed at 21 days was the highest.The mortality rate was 0.② In 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(P0.05),progressively increasing with time,and peaked at 28 days.Eleven MLD model mice died and the mortality rate was 30.56%.Conclusions The results of our study demonstrate that the mouse models developed at 21 days after BLM 200 mg/(kg·bw) injection is 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.