肠道尿酸排泄有助于急性痛风发作期间血清尿酸降低。

Intestinal uric acid excretion contributes to serum uric acid decrease during acute gout attack.

机构信息

Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China.

Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.

出版信息

Rheumatology (Oxford). 2023 Dec 1;62(12):3984-3992. doi: 10.1093/rheumatology/kead139.

DOI:10.1093/rheumatology/kead139

PMID:37042723

Abstract

OBJECTIVE

Spontaneous serum uric acid (SUA) decrease has been found in many patients during acute gout attacks, but its mechanism remains unclear.

METHODS

The spontaneous regulation of SUA during a gout attack and its possible causes were evaluated in patients with gout. The mechanism of the spontaneous SUA decrease was further studied in Caco2 cells and a monosodium urate (MSU)-induced gout model of wild-type mice and ABCG2-/- mice. The urate transport function of intestinal epithelial cells was detected by transwell culture of Caco2 cells. Expression of ATP-binding cassette super-family G member 2 (ABCG2), IL-1β and phosphoinositide 3-kinase (PI3K)/Akt was analysed using real-time PCR, western blotting, or immunofluorescence assays.

RESULTS

SUA decreased during acute gout attacks in both the gout patients and MSU-induced gouty mice. Increased serum CRP and IL-1β levels were correlated with the SUA decrease. Intestinal uric acid excretion and expression of ABCG2 were upregulated in the mice during acute gout attacks. In the ABCG2-/- mice, intestinal uric acid excretion significantly decreased during gout attacks. In an in vitro study of a transwell culture, ABCG2 and its upstream PI3K/Akt pathway were significantly upregulated in intestinal epithelial cells. However, ABCG2 expression and its associated intestinal uric acid transport were inhibited when PI3K/Akt was blocked by a PI3K inhibitor, LY294002.

CONCLUSIONS

Increased intestinal urate excretion resulted in spontaneous SUA downregulation during acute gout attacks. Inflammation-induced PI3K/Akt activation and ABCG2 expression in epithelial cells might contribute to the upregulation of intestinal uric acid excretion.

摘要

目的

在许多急性痛风发作患者中发现血清尿酸（SUA）自发降低，但机制尚不清楚。

方法

评估痛风患者痛风发作期间 SUA 的自发调节及其可能的原因。在 Caco2 细胞和野生型小鼠和 ABCG2-/-小鼠的单钠尿酸盐（MSU）诱导的痛风模型中进一步研究了 SUA 自发降低的机制。通过 Caco2 细胞的 Transwell 培养检测肠上皮细胞的尿酸转运功能。使用实时 PCR、western blot 或免疫荧光测定分析 ABCG2 超家族 G 成员 2（ABCG2）、白细胞介素 1β（IL-1β）和磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）的表达。

结果

痛风患者和 MSU 诱导的痛风性小鼠在急性痛风发作期间 SUA 降低。血清 CRP 和 IL-1β 水平升高与 SUA 降低相关。在急性痛风发作期间，小鼠的肠道尿酸排泄和 ABCG2 表达增加。在 ABCG2-/- 小鼠中，在痛风发作期间肠道尿酸排泄明显减少。在 Transwell 培养的体外研究中，肠上皮细胞中 ABCG2 及其上游 PI3K/Akt 途径显著上调。然而，当 PI3K 抑制剂 LY294002 阻断 PI3K/Akt 时，ABCG2 表达及其相关的肠道尿酸转运受到抑制。