Mechanism of intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease: An observational study

Xin,Xiaofeng; Dai,Wei; Wu,Jie; Fang,Liping; Zhao,Ming; Zhang,Pengpeng; Chen,Min

doi:10.3892/etm.2016.3493

September-2016 Volume 12 Issue 3

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September-2016 Volume 12 Issue 3

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Article Open Access

Mechanism of intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease: An observational study

Authors:
- Xiaofeng Xin
- Wei Dai
- Jie Wu
- Liping Fang
- Ming Zhao
- Pengpeng Zhang
- Min Chen
View Affiliations / Copyright

Affiliations: Department of Respiratory Medicine, Nanjing Jingling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, P.R. China

Copyright: © Xin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 1331-1336
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Published online on: June 30, 2016

https://doi.org/10.3892/etm.2016.3493
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Abstract

The aim of the present study was to investigate intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease (COPD). Male Sprague Dawley rats (n=40) were evenly randomized into control and COPD groups and the COPD model was established by regulated exposure to cigarette smoke for 6 months. Histopathological changes of the lung and intestinal tissues were detected by hematoxylin and eosin staining. Expression of the tight junction proteins occludin and zona occludens‑1 (ZO‑1) in the intestinal tissues were analyzed by western blotting, serum diamine oxidase (DAO) activity was detected by spectrophotometry, the urinary lactulose to mannitol ratio (L/M) was evaluated by high performance liquid chromatography, and intestinal tissue secretion of tumor necrosis factor (TNF)‑α, interferon (IFN)‑γ and interleukin (IL)‑8 were detected by ELISA. Lung histopathology revealed thinned alveolar walls, ruptured alveolar septa, enlarged and deformed alveoli, and the formation of bullae and emphysema due to alveolar fusion in the COPD group, while intestinal histopathology indicated clearly swollen intestines with darkened and gray mucosa, neutrophil infiltration of the intestinal mucosal and regional epithelial shedding. The occludin and ZO‑1 expression levels were significantly lower in the COPD group compared with those in the corresponding control group (P<0.05), while the urinary L/M ratio was significantly higher (P<0.05). Furthermore, the serum DAO activity and secretion of TNF‑α, IFN‑γ and IL‑8 in the intestinal tissues were significantly higher in the COPD group than in the control group (each P<0.05). Dysfunctional and structural changes were observed in the intestinal mucosal barrier in COPD model rats, which may be associated with the increased intestinal inflammatory responses.

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1	Abdool-Gaffar MS, Ambaram A, Ainslie GM, Bolliger CT, Feldman C, Geffen L, Irusen EM, Joubert J, Lalloo UG, Mabaso TT, et al: COPD Working Group: Guideline for the management of chronic obstructive pulmonary disease - 2011 update. S Afr Med J. 101:63–73. 2011.PubMed/NCBI
2	Mestecky J: The common mucosal immune system and current strategies for induction of immune responses in external secretions. J Clin Immunol. 7:265–276. 1987. View Article : Google Scholar : PubMed/NCBI
3	Garg P, Vijay-Kumar M, Wang L, Gewirtz AT, Merlin D and Sitaraman SV: Matrix metalloproteinase-9-mediated tissue injury overrides the protective effect of atrix metalloproteinase-2 during colitis. Am J Physiol Gastrointest Liver Physiol. 296:G175–G184. 2009. View Article : Google Scholar : PubMed/NCBI
4	Keely S, Talley NJ and Hansbro PM: Pulmonary-intestinal cross-talk in mucosal inflammatory disease. Mucosal Immunol. 5:7–18. 2012. View Article : Google Scholar : PubMed/NCBI
5	Rutten EP, Lenaerts K, Buurman WA and Wouters EF: Disturbed intestinal integrity in patients with COPD: Effects of activities of daily living. Chest. 145:245–252. 2014. View Article : Google Scholar : PubMed/NCBI
6	Zheng H, Liu Y, Huang T, Fang Z, Li G and He S: Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by sidestream cigarette smoke. Toxicol Lett. 189:225–234. 2009. View Article : Google Scholar : PubMed/NCBI
7	Li MM, Xin XF, Shao HT, Shi Y, Su X, Sun WK, Sun H and Fang LP: The expressions of nerve growth factor and its tyrosine kinase A receptor on alveolar macrophages in a rat model of chronic obstructive pulmonary disease. Zhonghua Jie He He Hu Xi Za Zhi. 35:601–605. 2012.(In Chinese). PubMed/NCBI
8	Liu H, Li W, Wang X, Li J and Yu W: Early gut mucosal dysfunction in patients with acute pancreatitis. Pancreas. 36:192–196. 2008. View Article : Google Scholar : PubMed/NCBI
9	Thomsen M, Dahl M, Lange P, Vestbo J and Nordestgaard BG: Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 186:982–988. 2012. View Article : Google Scholar : PubMed/NCBI
10	Shen L: Tight junctions on the move: Molecular mechanisms for epithelial barrier regulation. Ann NY Acad Sci. 7:9–18. 2012. View Article : Google Scholar
11	Odenwald MA and Turner JR: Intestinal permeability defects: Is it time to treat? Clin Gastroenterol Hepatol. 11:1075–1083. 2013. View Article : Google Scholar : PubMed/NCBI
12	Tian R, Tan JT, Wang RL, Xie H, Qian YB and Yu KL: The role of intestinal mucosa oxidative stress in gut barrier dysfunction of severe acute pancreatitis. Eur Rev Med Pharmacol Sci. 17:349–55. 2013.PubMed/NCBI
13	Cao M, Wang P, Sun C, He W and Wang F: Amelioration of IFN-γ and TNF-α-induced intestinal epithelial barrier dysfunction by berberine via suppression of MLCK-MLC phosphorylation signaling pathway. PLoS One. 8:e619442013. View Article : Google Scholar : PubMed/NCBI
14	Turner JR: Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 9:799–809. 2009. View Article : Google Scholar : PubMed/NCBI
15	Suzuki T: Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci. 70:631–659. 2013. View Article : Google Scholar : PubMed/NCBI
16	Yang S, Yu M, Sun L, Xiao W, Yang X, Sun L, Zhang C, Ma Y, Yang H, Liu Y, et al: Interferon-γ-induced intestinal epithelial barrier dysfunction by NF-kB/HIF-1α pathway. J Interferon Cytokine Res. 34:195–203. 2014. View Article : Google Scholar : PubMed/NCBI
17	Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M and Schulzke JD: TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFkappaB signaling. J Cell Sci. 123:4145–4155. 2010. View Article : Google Scholar : PubMed/NCBI
18	Ye D, Guo S, Al-Sadi R and Ma TY: MicroRNA regulation of intestinal epithelial tight junction permeability. Gastroenterology. 141:1323–1333. 2011. View Article : Google Scholar : PubMed/NCBI
19	Műzes G, Molnár B, Tulassay Z and Sipos F: Changes of the cytokine profile in inflammatory bowel diseases. World J Gastroenterol. 18:5848–5861. 2012. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Mechanism of intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease: An observational study

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Abstract

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