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慢性痛风的新型动物模型再现了人类疾病的病理特征。

New animal model of chronic gout reproduces pathological features of the disease in humans.

机构信息

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China.

Department of Orthopedic Surgery, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.

出版信息

RMD Open. 2023 Nov;9(4). doi: 10.1136/rmdopen-2023-003499.

Abstract

OBJECTIVES

Gout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop a novel chronic mouse model of gout that more closely mimics the progression of gout in humans.

METHODS

A novel chronic mouse model of gout was established by a simple method, which does not require high technical proficiency, predominantly involves daily intraperitoneal injections of potassium oxonate for approximately 4 months, combined with a high fat-diet and injections of acetic acid into the hind paws to facilitate the formation of monosodium urate (MSU). Arthritis scores and paw oedema were assessed, behavioural tests were conducted, and histopathological and imaging evaluations of the arthritic paw joints were performed.

RESULTS

After 4 months of induction, mice in the model group exhibited noticeable increases in arthritis severity, joint and cartilage damage, as well as bone erosion. Gomori's methenamine silver stain revealed the presence of MSU crystal deposition or tophi in the paw joints or ankle joints of up to 37.9% of the model mice (11 out of 29 mice). Moreover, treatment with benzbromarone effectively prevented the further development of gout or tophi formation in model mice.

CONCLUSIONS

Our model more accurately replicates the pathological features of gouty arthritis compared with gout induced by MSU crystal injections. Therefore, it is particularly suitable for further investigations into the pathogenesis of gout and also serves as a valuable platform for screening potential antigout agents.

摘要

目的

痛风作为最常见的炎症性关节炎形式,需要使用动物模型来研究其发病机制中的分子机制。因此,我们的目标是建立一种更接近人类痛风进展的新型慢性痛风小鼠模型。

方法

采用一种简单的方法建立了一种新型慢性痛风小鼠模型,该方法不需要很高的技术水平,主要包括每天腹腔注射氧嗪酸钾约 4 个月,同时给予高脂肪饮食,并向足底注射乙酸以促进单钠尿酸盐(MSU)的形成。评估关节炎评分和爪肿胀,进行行为测试,并对关节炎爪关节进行组织病理学和影像学评估。

结果

在诱导 4 个月后,模型组小鼠关节炎严重程度、关节和软骨损伤以及骨侵蚀明显增加。Gomori 的美蓝染色显示,多达 37.9%的模型小鼠(29 只小鼠中有 11 只)的爪关节或踝关节中存在 MSU 晶体沉积或痛风石。此外,苯溴马隆治疗可有效防止模型小鼠痛风或痛风石的进一步发展。

结论

与 MSU 晶体注射诱导的痛风相比,我们的模型更准确地模拟了痛风性关节炎的病理特征。因此,它特别适合进一步研究痛风的发病机制,也是筛选潜在抗痛风药物的有价值平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1bb/10660916/fef489681f0d/rmdopen-2023-003499f01.jpg

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