中国病理生理杂志2026，Vol.42Issue(4)：635-643,9.DOI:10.3969/j.issn.1000-4718.2026.04.002
肺上皮细胞特异性敲除Prtn3减缓博来霉素诱导的小鼠肺纤维化
Lung epithelial cell-specific knockout of Prtn3 attenuates bleomycin-in-duced pulmonary fibrosis in mice
摘要
Abstract
AIM:To investigate the impact of lung epithelial cell-specific knockout of proteinase 3(Prtn3)gene on bleomycin(BLM)-induced pulmonary fibrosis in mice.METHODS:Prtn3-floxed(Prtn3fl/fl)mice were generated using the CRISPR/Cas9 system.Eight to ten-week-old Prtn3fl/fl mice and wild-type(WT)C57BL/6J mice were used(n=10 per group).Lung epithelial cell-specific Prtn3 knockout was induced in Prtn3fl/fl mice via intranasal instillation of AAV6-CMV-Cre.A pulmonary fibrosis model was established by intranasal instillation of BLM at 5 mg/kg.The general condition and body weight changes of the mice were monitored dynamically.At the experimental endpoint,the mice were eutha-nized,and lung tissues were collected for fixation and analysis.Body weight changes,pathological alterations in lung tis-sues,and the levels of fibrosis markers and inflammatory factors were compared between the two groups.RESULTS:Fol-lowing BLM administration,the body weight of the mice decreased in both groups,more significantly in the WT+BLM group.Pathological analysis revealed that lung epithelial cell-specific knockout of Prtn3 significantly alleviated BLM-in-duced inflammatory infiltration(P<0.05)and collagen deposition(P<0.01).Furthermore,the protein expression levels of α-smooth muscle actin,collagen type I alpha 1 chain,fibronectin and transforming growth factor-β1 were significantly decreased(P<0.05 or P<0.01).The expression of macrophage marker F4/80 was also significantly suppressed(P<0.05).CONCLUSION:Lung epithelial cell-specific knockout of Prtn3 effectively attenuates the severity of BLM-induced pulmonary fibrosis in mice.关键词
蛋白酶3/转基因小鼠/肺纤维化/博来霉素/巨噬细胞Key words
proteinase 3/transgenic mice/pulmonary fibrosis/bleomycin/macrophages分类
医药卫生引用本文复制引用
李佳璐,程亚晨,王琳红,廖如兰,邵怡农,苏牧青,高肖慧,杜仁乐..肺上皮细胞特异性敲除Prtn3减缓博来霉素诱导的小鼠肺纤维化[J].中国病理生理杂志,2026,42(4):635-643,9.基金项目
国家自然科学基金资助项目(No.82203287) （No.82203287）
中国博士后科学基金资助项目(No.2022M722874) （No.2022M722874）
河南省医药科学研究院基本科研业务费(No.2025BP0203) （No.2025BP0203）
