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Autophagy Strengthens Intestinal Mucosal Barrier by Attenuating Oxidative Stress in Severe Acute Pancreatitis

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Abstract

Background

Intestinal mucosal barrier dysfunction can be caused by severe acute pancreatitis (SAP). It is normally associated with changes to mucosal autophagy and oxidative stress.

Objective

The aim of this study was to investigate the correlation between autophagy and oxidative stress on the intestinal mucosal barrier of SAP rat model.

Methods

SAP was induced by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. Bacterial translocation (BT) was detected by 16S rDNA sequencing analysis. Morphological alterations in the pancreas and gut were determined by hematoxylin–eosin staining. Oxidative stress status was determined by measuring the level of intestinal malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Western blot, RT-PCR, and immunofluorescent staining were preformed to analyze the expression of tight junction and autophagy proteins.

Results

According to the sequencing analysis, rats in SAP group were divided into BT (+) group (n = 9) and BT (−) group (n = 8). Pancreatic and intestinal injuries in SAP group were significantly higher than sham operation group. The content of MDA was clearly elevated, and SOD as well as GPx activities were decreased in BT (+) group as compared with BT (−) group. The expression of LC3II and Beclin1 in BT (−) group was higher than that observed in BT (+). In contrast, BT (+) group had a higher level of claudin-2 and a lower level of zonula occluden-1, occludin, and claudin-1.

Conclusion

These results suggest that activated autophagy may attenuate intestinal mucosal barrier dysfunction by preventing and reducing the oxidative stress in SAP.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China, Nos. 81270448 and 81470890.

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Authors and Affiliations

  1. Center of Colon and Rectum, Qingdao Municipal Hospital, Qingdao University, No. 1 Jiaozhou Road, Qingdao, 266011, Shandong Province, China

    Luqiao Huang, Yingjian Jiang, Jiang Wang & Dianliang Zhang

  2. Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong Province, China

    Zhenqing Sun

  3. Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong Province, China

    Zhengyu Gao

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  1. Luqiao Huang
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  2. Yingjian Jiang
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  5. Jiang Wang
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Correspondence to Dianliang Zhang.

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Huang, L., Jiang, Y., Sun, Z. et al. Autophagy Strengthens Intestinal Mucosal Barrier by Attenuating Oxidative Stress in Severe Acute Pancreatitis. Dig Dis Sci 63, 910–919 (2018). https://doi.org/10.1007/s10620-018-4962-2

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  • DOI: https://doi.org/10.1007/s10620-018-4962-2

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