Impaired intestinal barrier function in a mouse model of hyperuricemia

Guo,Yingjie; Li,Hailong; Liu,Zhen; Li,Changgui; Chen,Yunqing; Jiang,Chen; Yu,Yanan; Tian,Zibin

doi:10.3892/mmr.2019.10586

Impaired intestinal barrier function in a mouse model of hyperuricemia

Authors:
- Yingjie Guo
- Hailong Li
- Zhen Liu
- Changgui Li
- Yunqing Chen
- Chen Jiang
- Yanan Yu
- Zibin Tian
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Affiliations: Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China, Institute of Metabolic Diseases, Qingdao University, Qingdao, Shandong 266000, P.R. China
Published online on: August 12, 2019 https://doi.org/10.3892/mmr.2019.10586
Pages: 3292-3300
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Previous studies have demonstrated the effects of hyperuricemia on the damage to target organs, including the kidneys, joints and the heart. However, it is unclear whether hyperuricemia results in damage to the intestines. The aim of the present study was to investigate intestinal barrier dysfunction in a mouse model of hyperuricemia constructed by knocking out the urate oxidase (Uox) gene. The morphology of the intestine was assessed via hematoxylin and eosin, and alcian blue staining. The serum and intestinal tissue levels of uric acid, tumor necrosis factor (TNF)‑α and interleukin (IL)‑6, in addition to the presence of uremic toxins in the serum, were assessed. The levels of diamine oxidase (DAO), D‑lactate (D‑LAC) and endotoxins in the serum, which are markers of the intestinal permeability, were measured using ELISA. The expression of the intestinal tight junction proteins zona occludens‑1 (ZO‑1) and occludin were detected by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The Uox‑knockout mice spontaneously developed hyperuricemia. Histopathological analysis indicated notable intestinal defects including sparse villi, mucosal edema and a declining mucus layer in hyperuricemic mice. The expression levels of ZO‑1 and occludin in the intestines were downregulated, and the serum levels of DAO, D‑LAC and endotoxins were higher in the hyperuricemic mice, compared with control mice. The serum and intestinal tissue levels of IL‑6 and TNF‑α were significantly increased. Additionally, the expression levels of the serum uremic toxins, serum creatinine, blood urea nitrogen were significantly increased in hyperuricemic mice compared with the control mice, while only a marked increase in indoxyl sulfate (IS) and p‑cresol sulfate was reported. Collectively, the results of the present study suggested that intestinal barrier dysfunction and subsequent enhanced intestinal permeability may occur as a result of hyperuricemia in mice. Furthermore, we proposed that the loss of intestinal epithelium barrier function may be associated with uric acid‑induced inflammatory responses; however, further investigation is required.

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