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目的建立并评价博来霉素(BLM)诱导小鼠肺纤维化的动物模型。方法 SPF级雌性C57BL/6小鼠30只随机分为3组:模型组、假手术组、对照组。模型组小鼠气管注射BLM (5 mg/kg);假手术组小鼠气管注射等量生理盐水;对照组小鼠不做任何处理。各组小鼠在手术后第21天处死,收集肺组织制作病理切片,采用苏木精—伊红(HE)和马松染色评价各组小鼠肺纤维化程度。检测小鼠肺组织羟脯氨酸(HYP)质量分数、血清和肺组织中TGF-β1蛋白表达水平。结果模型组与对照组以及假手术组小鼠相比,其体重下降明显且小鼠存活率显著降低,手术后第21天存活小鼠肺组织HE和马松染色结果均显示严重的肺纤维化。而且,模型组小鼠肺组织HYP质量分数、血清以及肺组织TGF-β1蛋白表达水平均较对照组升高,差异具有统计学意义(P <0.01)。结论 BLM经气管给药可成功诱导小鼠肺纤维化模型,是较为理想的肺纤维化动物模型。
Abstract：Objective To establish and evaluate a mouse model of pulmonary fibrosis by intratracheal administration of bleomycin(BLM). Methods Thirty C57 BL/6 mice(female) were randomly divided into three groups: sham-operated group, model group and control group. The mice in the model group were given bleomycin(5 mg/kg), the sham-operated mice were injected with the same volume of saline, while the mice in the control group accepted no treatment. Mice were investigated and their weight was measured every day. Then they were sacrificed and their lungs collected on the 21 st day after operation, and serum was separated as well.After the lungs were fixed in formalin, and the paraffin sections were cut(5 μm thick). Hematoxylin-eosin(HE) and Masson trichrome staining was conducted to evaluate the extent of fibrosis. Hydroxyproline(HYP)content of lung tissue, the expression level of TGF-β1 from serum and lung tissue was tested. Results Compared with the control and sham-operated groups, mice of the BLM administration group showed a significantly severe lung fibrosis as measured by HE and Masson staining. Consistent with histological results, the HYP content and TGF-β1 expression levels from serum and lung tissue were much higher with statistical significance(P < 0.01) for mice of the model group. Conclusion The mouse model of pulmonary fibrosis was established successfully by intratracheal administration of the bleomycin, which might be the possible cause of the lung fibrosis in this model.
[1]Yan Li,Song Fan,Li Hua,et al.Submicron emulsion of cinnamaldehyde ameliorates bleomycin-induced idiopathic pulmonary fibrosis via inhibition of inflammation,oxidative stress and epithelial-mesenchymal transition[J].Biomedicine&Pharmacotherapy,2018,102:765-771
[2]Corte T,Bonella F,Crestani B,et al.Safety,tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis[J].Respiratory Research,2015,16(1):116
[3]Barratt S,Creamer A,Hayton C,et al.Idiopathic Pulmonary Fibrosis(IPF):an overview[J].Journal of Clinical Medicine,2018,7(8):21
[4]Martinez FJ,Collard HR,Pardo A,et al.Idiopathic pulmonary fibrosis[J].Nature Reviews Disease Primers,2017,3:17074
[5]Carrington R,Jordan S,Pitchford SC,et al.Use of animal models in IPF research[J].Pulmonary Pharmacology&Therapeutics,2018,51:73-78
[6]Renzoni E,Srihari V,Sestini P.Pathogenesis of idiopathic pulmonary fibrosis:review of recent findings[J].F1000Prime Reports,2014,6:69
[7]Mckleroy W,Lee TH,Atabai K.Always cleave up your mess:targeting collagen degradation to treat tissue fibrosis[J].American Journal of Physiology:Lung Cellular&Molecular Physiology,2013,304(11):L709-L721
[8]Aoshiba K,Tsuji T,Nagai A.Bleomycin induces cellular senescence in alveolar epithelial cells[J].European Respiratory Journal,2003,22(3):436-443
[9]King TE,Pardo A,Selman M.Idiopathic pulmonary fibrosis[J].The Lancet,2011,378(9807):1949-1961
[10]Chang W,Wei K,Ho L,et al.A critical role for the mTORC2 pathway in lung fibrosis[J].PLoS One,2014,9(8):e106155
[11]宋淑范,张晓晔.博来霉素诱导C57BL/6与ICR小鼠肺间质纤维化模型的比较[J].中国实验动物学报,2010,18(4):289-291
[12]宋桂芹,徐志伟,李泽,等.不同品系小鼠肺纤维化模型的比较研究[J].中国现代医学杂志,2017,27(4):13-16
[13]李丽娜,王华,周蕾,等.博来霉素诱导小鼠肺间质纤维化造模方式的选择[J].中国免疫学杂志,2010,26(3):254-257
[14]Degryse AL,Tanjore H,Xu XC,et al.Repetitive intratracheal bleomycin models several features of idiopathic pulmonary fibrosis[J].American Journal of Physiology:Lung Cellular&Molecular Physiology,2010,299(4):L442-L452
[15]Williamson JD,Sadofsky LR,Hart SP.The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis[J].Experimental Lung Research,2015,41:57-73
[16]Oga T,Matsuoka T,Yao C,et al.Prostaglandin F2αreceptor signaling facilitates bleomycin-induced pulmonary fibrosis independently of transforming growth factor-β[J].Nature Medicine,2009,15(12):1426-1430
[17]Degryse AL,Lawson WE.Progress toward improving animal models for idiopathic pulmonary fibrosis[J].The American Journal of the Medical Sciences,2011,341(6):444-449
[18]Gilhodes JC,JuléY,Kreuz S,et al.Quantification of pulmonary fibrosis in a bleomycin mouse model using automated histological image analysis[J].PLoS One,2017,12(1):e0170561
基本信息:
DOI：10.13885/j.issn.1000-2812.2019.06.007
中图分类号:R965;R-332
引用信息:
[1]卢锦辉,张丽,刘子豪等.博来霉素诱导小鼠肺纤维化模型的建立及评价[J].兰州大学学报(医学版),2019,45(06):37-42.DOI:10.13885/j.issn.1000-2812.2019.06.007.
基金信息:
甘肃省自然科学基金项目(18JR3RA279);; 中央高校基本科研业务费专项资金项目(223000/862612);; 家畜疫病病原生物学国家重点实验室开放基金项目(SKLVEB2017KFKT005)