Expression and pathological significance of neutrophil elastase and mucin 5AC in rats with chronic obstructive pulmonary disease_West China Medical Journal

Authors：

DING Chunxiao ¹ , LIU Xiaohu ¹ , LI Miao ¹ , LI Jianhua ² ,  FAN Yinglan ¹

1. Department of Pathology, Liaoning Province Chinese Medicine Research Institute, Shenyang, Liaoning 110034, P. R. China;
2. Department of Pathology, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P. R. China;

Corresponding?author：

FAN Yinglan, Email: 8719099@qq.com

Keywords：

Chronic obstructive pulmonary disease; Goblet cell; Mucus; Neutrophil elastase; Mucin 5AC

DOI：

10.7507/1002-0179.202103298

Video：

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Objective To investigate the expression and pathological significance of neutrophil elastase (NE) and mucin 5AC (MUC5AC) in chronic obstructive pulmonary disease (COPD) rats. Methods A total of 60 male specific pathogens free Sprague-Dawley rats were randomly divided into model group and blank group, each with 30 rats. The number of goblet cells and the positive expression of NE and MUC5AC were compared between the two groups by hematoxylin-eosin staining, alcianblue-periodic acid Schiff staining and immunohistochemical staining. Results No rats died accidentally during the experiment. The number of goblet cells was 57.93±7.79 in the model group and 6.80±3.19 in the blank group, and the difference between the two groups was statistically significant (t=?44.267, P<0.05). The median (lower quartile, upper quartile) of the positive expression score of NE was 0 (0, 0) in the blank group and 2 (2, 3) in the model group, the median (lower quartile, upper quartile) of the positive expression score of MUC5AC was 0 (0, 1) in the blank group and 2 (2, 2) in the model group, and the differences between the two groups were statistically significant (P<0.05).Conclusions The positive expression of NE, goblet cells, MUC5AC and mucus secretion in COPD model rats increases significantly. Perhaps NE and MUC5AC can be used as target interventions to inhibit mucus hypersecretion.

Citation： DING Chunxiao, LIU Xiaohu, LI Miao, LI Jianhua, FAN Yinglan. Expression and pathological significance of neutrophil elastase and mucin 5AC in rats with chronic obstructive pulmonary disease. West China Medical Journal, 2021, 36(9): 1227-1231. doi: 10.7507/1002-0179.202103298 Copy

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10.	劉婭欽, 馬麗, 劉琳. 慢性阻塞性肺疾病發病機制的研究進展. 臨床肺科雜志, 2016, 21(6): 1113-1117.
11.	李天浩, 韓晨旭, 王惠琴, 等. 基于 EGFR-MUC5AC 信號通路探討參魚化痰口服液干預慢性阻塞性肺疾病大鼠氣道黏液高分泌的機制. 陜西中醫, 2019, 40(8): 995-997, 1017.
12.	賴異, 李雯. 黏蛋白 MUC5AC 在慢性阻塞性肺疾病患者氣道中的表達及其臨床意義. 華中科技大學學報(醫學版), 2009, 38(3): 385-388.
13.	王駿, 李春盈, 劉治坤, 等. 慢性阻塞性肺疾病氣道黏液高分泌大鼠模型的建立. 心肺血管病雜志, 2014, 33(4): 592-595.
14.	曾春芳. NE 在 COPD 患者肺組織中的表達及其與巨噬細胞凋亡的相關性研究. 西南醫科大學學報, 2017, 40(4): 397-401.
15.	田君才, 杜國亮, 張桂霞. 人工免疫組化判定結果與灰度值相關性. 臨床與實驗病理學雜志, 2010, 26(1): 112-113.
16.	Negewo NA, Gibson PG, McDonald VM. COPD and its comorbidities: impact, measurement and mechanisms. Respirology, 2015, 20(8): 1160-1171.
17.	Divo M, Cote C, de Torres JP, et al. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2012, 186(2): 155-161.
18.	Decramer M, Janssens W. Chronic obstructive pulmonary disease and comorbidities. Lancet Respir Med, 2013, 1(1): 73-83.
19.	Faner R, Cruz T, López-Giraldo A, et al. Network medicine, multimorbidity and the lung in the elderly. Eur Respir J, 2014, 44(3): 775-788.
20.	Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome?. Lancet, 2007, 370(9589): 797-799.
21.	文富強, 申永春. 祛痰治療在慢性阻塞性肺疾病中臨床應用. 中華肺部疾病雜志(電子版), 2010, 3(4): 236-238.
22.	柏正平, 劉雨, 譚小寧, 等. 金水六君煎對慢性阻塞性肺疾病氣道黏液高分泌大鼠肺組織黏蛋白 5AC 及水通道蛋白 5 表達的影響. 中國中醫藥信息雜志, 2019, 26(8): 54-59.
23.	Gehrig S, Duerr J, Weitnauer M, et al. Lack of neutrophil elastase reduces inflammation, mucus hypersecretion, and emphysema, but not mucus obstruction, in mice with cystic fibrosis-like lung disease. Am J Respir Crit Care Med, 2014, 189(9): 1082-1092.
24.	李西西, 梁余良, 張娟, 等. 中性粒細胞彈性蛋白酶及其在急性肺損傷中的應用. 預防醫學論壇, 2017, 23(1): 74-76.
25.	Hayakawa T, Naruse S, Kitagawa M, et al. Elastase. Nihon Rinsho, 1995, 53(5): 1192-1197.
26.	Wang S, Guo H, Wang X, et al. Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury. Neural Regen Res, 2014, 9(15): 1453-1459.
27.	Atanasova KR, Reznikov LR. Strategies for measuring airway mucus and mucins. Respir Res, 2019, 20(1): 261.
28.	Lu W, Liu X, Wang T, et al. Elevated MUC1 and MUC5AC mucin protein levels in airway mucus of critical ill COVID-19 patients. J Med Virol, 2021, 93(2): 582-584.
29.	Krishn SR, Ganguly K, Kaur S, et al. Ramifications of secreted mucin MUC5AC in malignant journey: a holistic view. Carcinogenesis, 2018, 39(5): 633-651.

1. World Health Organization. The top 10 causes of death. (2020-12-09)[2021-07-23]. https://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death.
2. World Health Organization. Chronic obstructive pulmonary disease (COPD). (2021-06-21)[2021-07-23]. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd).
3. Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717.
4. 趙佳, 趙雅靜, 安艷春, 等. 慢性阻塞性肺疾病急性加重患者 30 d 內不同預后的臨床數據分析. 臨床急診雜志, 2020, 21(1): 65-69.
5. Adeloye D, Chua S, Lee C, et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J Glob Health, 2015, 5(2): 20415.
6. Vestbo J, Hurd SS, Agustí AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
7. 賈盼紅, 李琪, 熊曉嫚, 等. 基于中性粒細胞彈力蛋白酶介導的通路研究地膽頭干預慢性阻塞性肺疾病患者氣道黏液高分泌及療效觀察. 海南醫學院學報, 2021, 27(2): 101-104, 110.
8. Yang G, Wang Y, Zeng Y, et al. Rapid health transition in China, 1990-2010: findings from the global burden of disease study 2010. Lancet, 2013, 381(9882): 1987-2015.
9. 世界中醫藥學會聯合會. 國際中醫臨床實踐指南慢性阻塞性肺疾病. 世界中醫藥, 2020, 15(7): 1084-1092.
10. 劉婭欽, 馬麗, 劉琳. 慢性阻塞性肺疾病發病機制的研究進展. 臨床肺科雜志, 2016, 21(6): 1113-1117.
11. 李天浩, 韓晨旭, 王惠琴, 等. 基于 EGFR-MUC5AC 信號通路探討參魚化痰口服液干預慢性阻塞性肺疾病大鼠氣道黏液高分泌的機制. 陜西中醫, 2019, 40(8): 995-997, 1017.
12. 賴異, 李雯. 黏蛋白 MUC5AC 在慢性阻塞性肺疾病患者氣道中的表達及其臨床意義. 華中科技大學學報(醫學版), 2009, 38(3): 385-388.
13. 王駿, 李春盈, 劉治坤, 等. 慢性阻塞性肺疾病氣道黏液高分泌大鼠模型的建立. 心肺血管病雜志, 2014, 33(4): 592-595.
14. 曾春芳. NE 在 COPD 患者肺組織中的表達及其與巨噬細胞凋亡的相關性研究. 西南醫科大學學報, 2017, 40(4): 397-401.
15. 田君才, 杜國亮, 張桂霞. 人工免疫組化判定結果與灰度值相關性. 臨床與實驗病理學雜志, 2010, 26(1): 112-113.
16. Negewo NA, Gibson PG, McDonald VM. COPD and its comorbidities: impact, measurement and mechanisms. Respirology, 2015, 20(8): 1160-1171.
17. Divo M, Cote C, de Torres JP, et al. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2012, 186(2): 155-161.
18. Decramer M, Janssens W. Chronic obstructive pulmonary disease and comorbidities. Lancet Respir Med, 2013, 1(1): 73-83.
19. Faner R, Cruz T, López-Giraldo A, et al. Network medicine, multimorbidity and the lung in the elderly. Eur Respir J, 2014, 44(3): 775-788.
20. Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome?. Lancet, 2007, 370(9589): 797-799.
21. 文富強, 申永春. 祛痰治療在慢性阻塞性肺疾病中臨床應用. 中華肺部疾病雜志(電子版), 2010, 3(4): 236-238.
22. 柏正平, 劉雨, 譚小寧, 等. 金水六君煎對慢性阻塞性肺疾病氣道黏液高分泌大鼠肺組織黏蛋白 5AC 及水通道蛋白 5 表達的影響. 中國中醫藥信息雜志, 2019, 26(8): 54-59.
23. Gehrig S, Duerr J, Weitnauer M, et al. Lack of neutrophil elastase reduces inflammation, mucus hypersecretion, and emphysema, but not mucus obstruction, in mice with cystic fibrosis-like lung disease. Am J Respir Crit Care Med, 2014, 189(9): 1082-1092.
24. 李西西, 梁余良, 張娟, 等. 中性粒細胞彈性蛋白酶及其在急性肺損傷中的應用. 預防醫學論壇, 2017, 23(1): 74-76.
25. Hayakawa T, Naruse S, Kitagawa M, et al. Elastase. Nihon Rinsho, 1995, 53(5): 1192-1197.
26. Wang S, Guo H, Wang X, et al. Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury. Neural Regen Res, 2014, 9(15): 1453-1459.
27. Atanasova KR, Reznikov LR. Strategies for measuring airway mucus and mucins. Respir Res, 2019, 20(1): 261.
28. Lu W, Liu X, Wang T, et al. Elevated MUC1 and MUC5AC mucin protein levels in airway mucus of critical ill COVID-19 patients. J Med Virol, 2021, 93(2): 582-584.
29. Krishn SR, Ganguly K, Kaur S, et al. Ramifications of secreted mucin MUC5AC in malignant journey: a holistic view. Carcinogenesis, 2018, 39(5): 633-651.

West China Medical Journal

Expression and pathological significance of neutrophil elastase and mucin 5AC in rats with chronic obstructive pulmonary disease

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