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,广州 510000;2. 广州中医药大学第一临床医学院,广州 510000;3. 广州中医药大学岭南医学研究中心,广州 510000;4. 广东省中医临床研究院,广州 510000;5. 深圳市中西医结合医院,广东 深圳 518072;6. 深圳市宝安中医院,广东 深圳 518133

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Comparative study of idiopathic pulmonary fibrosis in mice induced by bleomycin of different concentrations
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1. the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510000, China; 2. the First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China; 3. Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou 510000, China; 4. Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou 510000, China; 5. Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen 518072, China; 6. Shenzhen Bao’an Hospital of Traditional Chinese Medicine, Shenzhen 518133, China

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    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(1.5 mg/kg BLM)、中(2.5 mg/kg BLM)、高(3.5 mg/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、体质量、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,体质量呈下降趋势,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、Fn1和Col1a1的mRNA水平表达上调(P<0.001),相应蛋白表达也显著上调(P<0.05),炎症因子Tgfb1的mRNA表达增加(P<0.0001)。 结论 1.5、2.5和3.5 mg/kg的博来霉素均可诱导C57BL/6J小鼠IPF,结合生存率、体质量和肺系数变化、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,2.5 mg/kg博来霉素为诱导的IPF小鼠的最适宜浓度。

    Abstract:

    Objective To investigate the establishment and evaluation of an idiopathic pulmonary fibrosis (IPF) mouse model induced by the intratracheal infusion of bleomycin (BLM) of different concentrations. Methods Male C57BL/6J mice were randomly divided into a control group, Model-L group (1.5 mg/kg, BLM), Model-M group (2.5 mg/kg, BLM), and Model-H group (3.5 mg/kg, BLM). An IPF mouse model was constructed by onetime intratracheal infusion of BLM. The general status, body mass, survival rate, and lung coefficient of mice in different groups were compared. Pathological changes in lung tissue, the hydroxyproline content, fibrosis markers and inflammatory factor levels were observed. Results Compared with the control group, the survival rate decreased and body weight showed a downward trend in the low-, medium-, and high-dose model groups, with significant increases in lung coefficients. Inflammatory infiltration (P<0.01) and collagen deposition (P<0.0001) were observed in the lung tissues of all model groups. Hydroxyproline levels in lung tissue and serum were significantly elevated (P<0.05). The mRNA levels of fibrosis markers α-Sma, Fn1, and Col1a1 were upregulated (P<0.001), with significant increases in corresponding protein expression (P<0.05). The mRNA expression of the inflammatory factor Tgfb1 also increased (P<0.0001). Conclusions 1.5, 2.5 and 3.5 mg/kg BLM can induce an IPF model in C57BL/6J mice. Based on the Results observed for survival rate, body mass, lung coefficient changes, lung tissue gross and pathological changes, and fibrosis-related biomarkers, 2.5 mg/kg BLM is the optimal concentration for inducing an IPF mouse model.

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张欣欣,谢铱子,黄慧婷,江勇,李航,廖钢,温武金,詹少锋,黄秀芳.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[J].中国实验动物学报,2025,33(5):673~683.

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  • 收稿日期:2024-07-23
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  • 在线发布日期: 2025-07-08
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