Experimental study on establishment of mouse model of combined pulmonary fibrosis and emphysema_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 LI Feng , XU Mengmeng , WANG Muyun , CHEN Yuqin , ZHANG Hai , ZHANG Yanbei

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P. R. China;

Corresponding author：

LI Feng, Email: lifeng741@aliyun.com

Keywords：

Fine particulate matter; Ozone; Mouse model; Combined pulmonary fibrosis and emphysema

DOI：

10.7507/1671-6205.201806007

Video：

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ObjectiveTo study the possbility of using intranasal instillation of fine particulate matter (PM_2.5) combined with inhalation of ozone (O₃) to establish mouse model of combined pulmonary fibrosis and emphysema (CPFE), and to provide a reference for the establishment of CPFE model.MethodsMale C57/BL6 mice were divided randomly into phosphate buffer saline (PBS) intranasal instillation+air inhalation group, PBS intranasal instillation+O₃ inhalation group and PM_2.5 intranasal instillation+O₃ inhalation group, with 8 mice in each group. The mice were intranasally instilled with PBS or PM_2.5 suspension (7.8 mg/kg) followed by air or ozone inhalation 24 hours later, twice a week over 8 weeks. Lung function, bronchoalveolar lavage fluid (BALF) cell counts and classification were detected, the pathological changes of lung tissues in hematoxylin-eosin staining were observed, including inflammation scores and mean linear intercept (Lm). The thickness of collagen deposition in subepithelium was measured in lung tissues in Masson staining, and simultaneously hydroxyproline contents in lung tissues were determined.ResultsCompared to PBS instillation+air inhalation group, inspiratory capacity (IC), total lung capacity (TLC) and chord compliance (Cchord) were increased, FEV₂₅ (the forced expiratory volume at 25 ms)/FVC (forced vital capacity) was decreased, total cell counts in BALF, Lm and lung inflammatory scores were increased, the thickness of the subepithelial collagen layer (SEc/Pbm) or hydroxyproline contents was not changed in PBS instillation +O₃ inhalation group; IC was decreased, functional residual capacity (FRC) was increased, TLC was increased, Cchord was decreased, FEV₂₅/FVC and FEV₅₀ (the forced expiratory volume at 50 ms)/FVC were decreased, total cell counts in BALF, Lm, lung inflammatory scores, SEc/Pbm and hydroxyproline contents were increased in PM_2.5 instillation+O₃ inhalation group. Compared to PBS instillation+O₃ inhalation group, IC was decreased, FRC was increased, Cchord was decreased, FEV₂₅/FVC and FEV₅₀/FVC were decreased, total cell counts in BALF, Lm, lung inflammatory scores, SEc/Pbm and hydroxyproline contents were increased in PM_2.5 instillation +O₃ inhalation group.ConclusionCPFE mouse model can be successfully established by PM_2.5 intranasal instillation combined with ozone inhalation for consecutive 8 weeks.

Citation： LI Feng, XU Mengmeng, WANG Muyun, CHEN Yuqin, ZHANG Hai, ZHANG Yanbei. Experimental study on establishment of mouse model of combined pulmonary fibrosis and emphysema. Chinese Journal of Respiratory and Critical Care Medicine, 2018, 17(6): 604-608. doi: 10.7507/1671-6205.201806007 Copy

1.	Zhang L, Zhang C, Dong F, et al. Combined pulmonary fibrosis and emphysema: a retrospective analysis of clinical characteristics, treatment and prognosis. BMC Pulm Med, 2016, 16(1): 137.
2.	Cottin V, Nunes H, Brillet PY, et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J, 2005, 26(4): 586-593.
3.	Chen R, Yin P, Meng X, et al. Fine particulate air pollution and daily mortality. a nationwide analysis in 272 Chinese cities. Am J Respir Crit Care Med, 2017, 196(1): 73-81.
4.	Sack C, Vedal S, Sheppard L, et al. Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air-lung study. Eur Respir J, 2017, 50(6): pii: 1700559.
5.	Zhang WG, Wu SS, He L, et al. Comparative study of two models of combined pulmonary fibrosis and emphysema in mice. Acta Histochem, 2017, 119(3): 244-251.
6.	Triantaphyllopoulos K, Hussain F, Pinart M, et al. A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice. Am J Physiol Lung Cell Mol Physiol, 2011, 300(5): L691-L700.
7.	Li F, Zhang P, Zhang M, et al. Hydrogen sulfide prevents and partially reverses ozone-induced features of lung inflammation and emphysema in mice. Am J Respir Cell Mol Biol, 2016, 55(1): 72-81.
8.	Jiang S, Bo L, Du X, et al. CARD9-mediated ambient PM_2.5-induced pulmonary injury is associated with Th17 cell. Toxicol Lett, 2017, 273: 36-43.
9.	Knudsen L, Weibel ER, Gundersen HJ, et al. Assessment of air space size characteristics by intercept (chord) measurement: an accurate and efficient stereological approach. J Appl Physiol (1985), 2010, 108(2): 412-421.
10.	Falcon-Rodriguez CI, Osornio-Vargas AR, Sada-Ovalle I, et al. Aeroparticles, composition, and lung diseases. Front Immunol, 2016, 7: 3.
11.	Fiordelisi A, Piscitelli P, Trimarco B, et al. The mechanisms of air pollution and particulate matter in cardiovascular diseases. Heart Fail Rev, 2017, 22(3): 337-347.
12.	Rice MB, Ljungman PL, Wilker EH, et al. Long-term exposure to traffic emissions and fine particulate matter and lung function decline in the Framingham heart study. Am J Respir Crit Care Med, 2015, 191(6): 656-664.
13.	Zheng Z, Zhang X, Wang J, et al. Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models. J Hepatol, 2015, 63(6): 1397-1404.
14.	Bromberg PA. Mechanisms of the acute effects of inhaled ozone in humans. Biochim Biophys Acta, 2016, 1860(12): 2771-2781.
15.	Li P, Wu G. Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth. Amino Acids, 2018, 50(1): 29-38.

1. Zhang L, Zhang C, Dong F, et al. Combined pulmonary fibrosis and emphysema: a retrospective analysis of clinical characteristics, treatment and prognosis. BMC Pulm Med, 2016, 16(1): 137.
2. Cottin V, Nunes H, Brillet PY, et al. Combined pulmonary fibrosis and emphysema: a distinct underrecognised entity. Eur Respir J, 2005, 26(4): 586-593.
3. Chen R, Yin P, Meng X, et al. Fine particulate air pollution and daily mortality. a nationwide analysis in 272 Chinese cities. Am J Respir Crit Care Med, 2017, 196(1): 73-81.
4. Sack C, Vedal S, Sheppard L, et al. Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air-lung study. Eur Respir J, 2017, 50(6): pii: 1700559.
5. Zhang WG, Wu SS, He L, et al. Comparative study of two models of combined pulmonary fibrosis and emphysema in mice. Acta Histochem, 2017, 119(3): 244-251.
6. Triantaphyllopoulos K, Hussain F, Pinart M, et al. A model of chronic inflammation and pulmonary emphysema after multiple ozone exposures in mice. Am J Physiol Lung Cell Mol Physiol, 2011, 300(5): L691-L700.
7. Li F, Zhang P, Zhang M, et al. Hydrogen sulfide prevents and partially reverses ozone-induced features of lung inflammation and emphysema in mice. Am J Respir Cell Mol Biol, 2016, 55(1): 72-81.
8. Jiang S, Bo L, Du X, et al. CARD9-mediated ambient PM_2.5-induced pulmonary injury is associated with Th17 cell. Toxicol Lett, 2017, 273: 36-43.
9. Knudsen L, Weibel ER, Gundersen HJ, et al. Assessment of air space size characteristics by intercept (chord) measurement: an accurate and efficient stereological approach. J Appl Physiol (1985), 2010, 108(2): 412-421.
10. Falcon-Rodriguez CI, Osornio-Vargas AR, Sada-Ovalle I, et al. Aeroparticles, composition, and lung diseases. Front Immunol, 2016, 7: 3.
11. Fiordelisi A, Piscitelli P, Trimarco B, et al. The mechanisms of air pollution and particulate matter in cardiovascular diseases. Heart Fail Rev, 2017, 22(3): 337-347.
12. Rice MB, Ljungman PL, Wilker EH, et al. Long-term exposure to traffic emissions and fine particulate matter and lung function decline in the Framingham heart study. Am J Respir Crit Care Med, 2015, 191(6): 656-664.
13. Zheng Z, Zhang X, Wang J, et al. Exposure to fine airborne particulate matters induces hepatic fibrosis in murine models. J Hepatol, 2015, 63(6): 1397-1404.
14. Bromberg PA. Mechanisms of the acute effects of inhaled ozone in humans. Biochim Biophys Acta, 2016, 1860(12): 2771-2781.
15. Li P, Wu G. Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth. Amino Acids, 2018, 50(1): 29-38.

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Experimental study on establishment of mouse model of combined pulmonary fibrosis and emphysema

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