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丁酸钠对高尿酸血症小鼠肠道屏障损伤及尿酸降低的保护作用。

Protective effect of sodium butyrate on intestinal barrier damage and uric acid reduction in hyperuricemia mice.

机构信息

Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Plastic Surgery Institute of Weifang Medical University, Weifang, China.

出版信息

Biomed Pharmacother. 2023 May;161:114568. doi: 10.1016/j.biopha.2023.114568. Epub 2023 Mar 20.

DOI:10.1016/j.biopha.2023.114568
PMID:36948133
Abstract

PURPOSE

The goal of this study was to examine the role of sodium butyrate in preserving the intestinal mucosal barrier and reducing hyperuricemia (HUA).

METHODS

First, we established a mouse model of HUA via intraperitoneal injection of potassium oxonate together with a yeast-rich diet to detect the levels of serum uric acid (UA) and fecal short-chain fatty acids (SCFAs). Then, in vitro, different concentrations of UA and sodium butyrate (NaB) were used to treat LS174T and Caco2 cells. The effects of UA and NaB on the gut barrier were determined based on the expression levels of MUC2, ZO-1, and Occludin.Finally, C57BL/6 mice were used to model HUA, and these mice were administered 200 mg·kg·d NaB by gavage to counter the HUA. The effect of NaB on HUA in the intestinal tract was elucidated by determining serum UA levels, inflammatory parameters, epithelial barrier integrity, and via histological analysis.

RESULTS

The data showed that the content of fecal SCFAs in HUA mice decreased. Additionally, in LS174T and Caco2 cells, NaB reversed the decrease of ZO-1, Occludin, and MUC2 protein expression caused by high UA levels. Furthermore, NaB decreased serum UA of HUA mice, and reversed both the decreased expression of MUC2, ZO-1, Occludin, and ABCG2 proteins and the increased level of inflammatory factors in the intestinal tissues of these mice.

CONCLUSION

The HUA mouse model showed intestinal barrier damage. NaB protected the intestinal barrier of HUA mice and reduced the serum UA level.

摘要

目的

本研究旨在探讨丁酸钠在维持肠道黏膜屏障和降低高尿酸血症(HUA)中的作用。

方法

首先,我们通过腹腔注射氧嗪酸钾和酵母丰富的饮食建立了 HUA 小鼠模型,以检测血清尿酸(UA)和粪便短链脂肪酸(SCFAs)水平。然后,在体外,我们使用不同浓度的 UA 和丁酸钠(NaB)处理 LS174T 和 Caco2 细胞。根据 MUC2、ZO-1 和 Occludin 的表达水平,确定 UA 和 NaB 对肠道屏障的影响。最后,我们使用 C57BL/6 小鼠建立 HUA 模型,并通过灌胃给予 200mg·kg·d NaB 来对抗 HUA。通过测定血清 UA 水平、炎症参数、上皮屏障完整性和组织学分析,阐明 NaB 对肠道 HUA 的作用。

结果

数据显示,HUA 小鼠粪便中 SCFAs 的含量减少。此外,在 LS174T 和 Caco2 细胞中,NaB 逆转了高 UA 水平导致的 ZO-1、Occludin 和 MUC2 蛋白表达减少。此外,NaB 降低了 HUA 小鼠的血清 UA,并逆转了肠道组织中 MUC2、ZO-1、Occludin 和 ABCG2 蛋白表达减少和炎症因子水平升高。

结论

HUA 小鼠模型表现出肠道屏障损伤。NaB 保护 HUA 小鼠的肠道屏障并降低血清 UA 水平。

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