博来霉素联合猪胰弹性蛋白酶诱导的小鼠肺纤维化合并肺气肿模型的建立OA

Objective To establish a mouse model of combined pulmonary fibrosis and emphysema(CPFE)in-duced by intratracheal instillation of bleomycin(BLM)combined with porcine pancreatic elastase(PPE).Methods Male C57BL/6 mice were randomly divided into a control group and an experimental group.Mice in the experimental group received intratracheal instillation of a suspension of BLM(2.5 mg/kg)and PPE(1.5 U/100 g).The control group received instillation of phosphate-buffered saline(PBS).After four weeks,lung function was assessed.Histopathological changes in lung tissue were observed using hematoxylin-eosin staining,and the mean linear intercept(MLI)was measured.Fibrosis severity was evaluated using Masson's trichrome staining,and the subepithelial collagen deposition thickness(SEc/Pbm)in the airways was determined.Additionally,hydroxypro-line content in lung tissue was measured.Results Compared with the control group,the experimental group showed an increase in functional residual capacity(FRC),a decrease in FEV50(forced expiratory volume at 50 ms)/FVC and maximum mid-expiratory flow(MMEF),a trend toward decreased dynamic pulmonary compliance(Cdyn),no significant change in inspiratory capacity(IC),and no significant change in chord compli-ance(Cchord).Histologically,the experimental group exhibited enlarged alveolar septa and alveolar wall disruption in some lung regions,along with significant collagen deposition in the airways and parts of the lung pa-renchyma.Furthermore,MLI,SEc/Pbm,and hydroxyproline content were all significantly increased.Conclusions Intratracheal instillation of BLM combined with PPE successfully establishes a CPFE model in C57BL/6 mice within four weeks,characterized by both emphysema-like damage and fibrotic changes.This model provides an ex-perimental basis for future research on the mechanisms underlying the development and progression of CPFE and for evaluating intervention strategies.