中国病理生理杂志2025,Vol.41Issue(12):2489-2496,8.DOI:10.3969/j.issn.1000-4718.2025.12.025
博来霉素致小鼠肺纤维化的病理演变研究
Dynamic pathological characterization of bleomycin-induced pulmonary fibrosis in a murine model
摘要
Abstract
AIM:To systematically characterize the pathological progression of bleomycin(BLM)-induced pulmonary fibrosis in a murine model.METHODS:Thirty SPF-grade male C57BL/6J mice were randomly divided into a control group(n=6)or BLM intervention groups with varying durations(BLM-7 d,BLM-14 d,BLM-21 d group;n=8 per group)using the random number table method.A single intratracheal drip of BLM(5 mg/kg)was used to intervene for 0,7,14 and 21 days.Changes in body weight were recorded,and survival curves were plotted.Hematoxylin and eosin(HE)staining and scoring of alveolitis in lung tissues were performed.Masson staining(Masson)and scoring of fibrosis in lung tissues were conducted.A cell counter was used to analyze the number of cells in bronchoalveolar lavage fluid(BALF).The Bradford protein concentration assay kit was used to detect the total protein concentration of BALF.A hy-droxyproline(HYP)assay kit was used to measure the HYP content of lung tissue.Ki67 immunofluorescence staining was used to detect the proliferation of type Ⅱ alveolar epithelial cells(AT2).RESULTS:The weight of mice in control group increased steadily,and the survival rate was 100%.The weight of model group showed dynamic changes,reaching the lowest value on day 7(P<0.01),and then gradually rebounded.The survival rate of all groups in the model was 75%.BALF cell counts,BALF total protein concentration,and HE staining revealed severe alveolar structural destruction and inflammatory infiltration on days 7 to 14(P<0.01),peaking at day 14.Masson staining and HYP content demonstrated in-creased collagen deposition in lung tissues from days 14 to 21,with widespread fibrotic lesions at day 14 and dual patholog-ical changes(aggravation/repair)in fibrotic regions by day 21.SPC/Ki67 co-staining showed significantly reduced AT2 cell proliferation on days 7 and 14(P<0.01).Foci of abnormal proliferation appeared in the lesion area on day 21 of BLM intervention,and in some areas,it even exceeded the level of the control group.CONCLUSION:BLM-induced pulmo-nary fibrosis in mice shows characteristic pathological processes:acute inflammatory phase(BLM-7 d)→ inflammatory-fi-brotic transition phase(BLM-14 d)→ reparative phase(BLM-21 d).关键词
博来霉素/肺纤维化小鼠模型/炎症/肺泡上皮修复Key words
bleomycin/pulmonary fibrosis mouse model/inflammation/alveolar epithelial repair分类
医药卫生引用本文复制引用
卢俞奇,吴泳佳,赵鹏,李建生,张琴..博来霉素致小鼠肺纤维化的病理演变研究[J].中国病理生理杂志,2025,41(12):2489-2496,8.基金项目
国家自然科学基金资助项目(No.82304918) (No.82304918)
河南省高等学校重点科研项目(No.24A360018) (No.24A360018)