不同浓度博来霉素诱导特发性肺纤维化小鼠模型的比较研究
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1.广州中医药大学第一附属医院;2.深圳市中西医结合医院

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广东省中药管理局项目(No.20221144);深圳市“医疗卫生三名工程”项目(No.SZZYSM202206013);广州市科技计划项目(No.202201020457);国家中医优势专科建设项目(广州中医药大学第一附属医院肺病科);广东省重点科室(中西医协同科室)建设项目;广州中医药大学青年拔尖人才(团队)“揭榜挂帅”项目。


Comparative study of idiopathic pulmonary fibrosis induced by bleomycin at different concentrations in mice
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1.The First Affiliated Hospital of Guangzhou University of Chinese Medicine;2.Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine;3.Shenzhen Bao '4.'5.an Hospital of Traditional Chinese Medicine

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administration of Traditional Chinese Medicine of Guangdong Province (Grant no. 20221144) , the Sanming Project of Medicine in Shenzhen (Grant no. SZZYSM202206013), the Guangzhou Science and Technology Project (202201020457), National Chinese Medicine Specialty Construction Project (Department of Lung Disease, the First Affiliated Hospital of Guangzhou University of Chinese Medicine) , Guangdong Province key department (Chinese and Western medicine coordination department) construction project;Guangzhou University of Chinese Medicine young top talents (team)

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    摘要:

    摘要:目的 探讨气管内滴注不同浓度的博来霉素(Bleomycin, BLM)诱导特发性肺纤维化(Idiopathic pulmonary fibrosis,IPF)小鼠的建立与评价。方法 雄性C57BL/6J小鼠随机分为对照组、模型低(1.5mg/kg BLM)、中(2.5mg/kg BLM)、高(3.5mg/kg BLM)剂量组。采用一次性气管内滴注博来霉素构建IPF小鼠,比较不同组小鼠的一般状态、体重、生存率和肺系数,观察小鼠肺组织病理学改变、羟脯氨酸、纤维化标志物和炎症因子水平。结果 与对照组相比,模型低、中、高剂量组生存率降低,体重呈下降趋势(P<0.001),肺系数均显著增加;模型低、中、高剂量组肺组织出现炎性浸润(P<0.01)和胶原沉积(P<0.0001);肺组织和血清中的羟脯氨酸显著升高(P<0.05);纤维化标志物α-SMA、FN、COL1A1的mRNA和蛋白水平表达上调,炎症因子TGF-β1的mRNA表达增加。结论 1.5、2.5和3.5mg/kg的博来霉素均可诱导C57BL/6J小鼠IPF,结合生存率、体重和肺系数变化、肺组织大体观和病理学改变、纤维化和炎症相关指标等结果,2.5mg/kg 博来霉素为诱导的IPF小鼠的最适宜浓度。

    Abstract:

    Abstract: Objective To investigate the establishment and evaluation of intratracheal infusion of bleomycin with different concentrations on the induced idiopathic pulmonary fibrosis (IPF) mouse model. Methods Male C57BL/6J mice were randomly divided into the control group, Model-L group (1.5mg/kg, BLM), Model-M group (2.5mg/kg, BLM) and Model-H group (3.5mg/kg, BLM). IPF mouse model was constructed by one-time intratracheal infusion of bryomycin. The general status, body weight, survival rate and lung coefficient of mice in different groups were compared, and pathological changes of lung tissue, hydroxyproline content ,fibrotic markers and inflammatory factors were observed. Results Compared with the control group, the survival rate of the low, medium, and high dose groups in the model decreased, and body weight showed a downward trend (P<0.001), with a significant increase in lung coefficient. Additionally, inflammatory infiltration (P<0.01) and collagen deposition (P<0.0001) were exhibited in the lung tissues of the low, medium, and high dose groups. Hydroxyproline levels in lung tissue and serum were significantly elevated (P<0.05). The expression of fibrotic markers α-SMA, FN, COL1A1 at both mRNA and protein levels was upregulated, and the mRNA expression of the inflammatory factor TGF-β1 increased. Conclusion 1.5, 2.5 and 3.5mg/kg bleomycin can induce IPF model of C57BL/6J mice. Combined with the results of survival rate, body weight and lung coefficient changes, lung tissue gross and pathological changes, fibrosis related biomarkers, 2.5mg/kg bleomycin is the optimal concentration for IPF induced mouse model.

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  • 收稿日期:2024-07-23
  • 最后修改日期:2024-11-29
  • 录用日期:2025-01-22
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