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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11.	李天浩, 韩晨旭, 王惠琴, 等. 基于 EGFR-MUC5AC 信号通路探讨参鱼化痰口服液干预慢性阻塞性肺疾病大鼠气道黏液高分泌的机制. 陕西中医, 2019, 40(8): 995-997, 1017.
12.	赖异, 李雯. 黏蛋白 MUC5AC 在慢性阻塞性肺疾病患者气道中的表达及其临床意义. 华中科技大学学报(医学版), 2009, 38(3): 385-388.
13.	王骏, 李春盈, 刘治坤, 等. 慢性阻塞性肺疾病气道黏液高分泌大鼠模型的建立. 心肺血管病杂志, 2014, 33(4): 592-595.
14.	曾春芳. NE 在 COPD 患者肺组织中的表达及其与巨噬细胞凋亡的相关性研究. 西南医科大学学报, 2017, 40(4): 397-401.
15.	田君才, 杜国亮, 张桂霞. 人工免疫组化判定结果与灰度值相关性. 临床与实验病理学杂志, 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.
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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.
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21.	文富强, 申永春. 祛痰治疗在慢性阻塞性肺疾病中临床应用. 中华肺部疾病杂志(电子版), 2010, 3(4): 236-238.
22.	柏正平, 刘雨, 谭小宁, 等. 金水六君煎对慢性阻塞性肺疾病气道黏液高分泌大鼠肺组织黏蛋白 5AC 及水通道蛋白 5 表达的影响. 中国中医药信息杂志, 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, 张娟, 等. 中性粒细胞弹性蛋白酶及其在急性肺损伤中的应用. 预防医学论坛, 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. 赵佳, 赵雅静, 安艳春, 等. 慢性阻塞性肺疾病急性加重患者 30 d 内不同预后的临床数据分析. 临床急诊杂志, 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. 贾盼红, 李琪, 熊晓嫚, 等. 基于中性粒细胞弹力蛋白酶介导的通路研究地胆头干预慢性阻塞性肺疾病患者气道黏液高分泌及疗效观察. 海南医学院学报, 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. 世界中医药学会联合会. 国际中医临床实践指南慢性阻塞性肺疾病. 世界中医药, 2020, 15(7): 1084-1092.
10. 刘娅钦, 马丽, 刘琳. 慢性阻塞性肺疾病发病机制的研究进展. 临床肺科杂志, 2016, 21(6): 1113-1117.
11. 李天浩, 韩晨旭, 王惠琴, 等. 基于 EGFR-MUC5AC 信号通路探讨参鱼化痰口服液干预慢性阻塞性肺疾病大鼠气道黏液高分泌的机制. 陕西中医, 2019, 40(8): 995-997, 1017.
12. 赖异, 李雯. 黏蛋白 MUC5AC 在慢性阻塞性肺疾病患者气道中的表达及其临床意义. 华中科技大学学报(医学版), 2009, 38(3): 385-388.
13. 王骏, 李春盈, 刘治坤, 等. 慢性阻塞性肺疾病气道黏液高分泌大鼠模型的建立. 心肺血管病杂志, 2014, 33(4): 592-595.
14. 曾春芳. NE 在 COPD 患者肺组织中的表达及其与巨噬细胞凋亡的相关性研究. 西南医科大学学报, 2017, 40(4): 397-401.
15. 田君才, 杜国亮, 张桂霞. 人工免疫组化判定结果与灰度值相关性. 临床与实验病理学杂志, 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. 文富强, 申永春. 祛痰治疗在慢性阻塞性肺疾病中临床应用. 中华肺部疾病杂志(电子版), 2010, 3(4): 236-238.
22. 柏正平, 刘雨, 谭小宁, 等. 金水六君煎对慢性阻塞性肺疾病气道黏液高分泌大鼠肺组织黏蛋白 5AC 及水通道蛋白 5 表达的影响. 中国中医药信息杂志, 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, 张娟, 等. 中性粒细胞弹性蛋白酶及其在急性肺损伤中的应用. 预防医学论坛, 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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