Wang Yufang, Zhang Ya, Yu Zhengrong, Bai Yige, Zhu Mengxing, Lei Yan, Dong Baoli, Zhang Qiyao, Gu Qingyang, Xiang Jian
In Vivo Pharmacology Unit (IVPU), WuXi Biology, WuXi AppTec, China.
Curr Protoc. 2025 Mar;5(3):e70114. doi: 10.1002/cpz1.70114.
Gout is a chronic disease caused by the deposition of monosodium urate monohydrate (MSU) crystals within the body, particularly in one or more joints, which can lead to sudden severe attacks of pain, swelling, redness, and tenderness, known as gout flares. Historically termed the "disease of kings," gout is one of the oldest joint diseases and remains the most common form of inflammatory arthritis haunting humans in the 21 century. It is associated with cardiovascular, metabolic, and renal comorbidities and can lead to reduced mobility and impaired physical function and contributing to work absenteeism. Given its increasing global incidence, novel therapies for gouty arthritis disease are urgently needed. Experimental gout models are indispensable tools for deciphering disease pathogenesis and evaluating the efficacy and side effect of newly developed therapeutics at preclinical stage. Herein, we described a series of highly reproducible acute gout flare and air pouch models in rodents and rabbits that can be used to address various scientific questions relevant to pathological changes and immune responses during and after a gout attack. Animal gout flare models, elicited by MSU crystals, mimic the main histopathological features of human gouty arthritis, including damage to cartilage and joint swelling. Meanwhile, air pouch models serve as a tool to evaluate robust inflammatory cytokine secretion and neutrophil infiltration. This article provides a detailed description of procedures and troubleshooting tips required to reproducibly induce gout flare and air pouch models in animals and critically evaluate the pathogenesis of the disease. © 2025 Wiley Periodicals LLC. Basic Protocol 1: Preparation of monosodium urate crystalline Basic Protocol 2: Development of MSU-induced gout flare model in mice Support Protocol 1: Histological assessment of mouse ankle tissues Basic Protocol 3: Development of MSU-induced gout flare model in rats Basic Protocol 4: Development of MSU-induced gout flare model in rabbits Basic Protocol 5: Development and validation of reference articles in MSU-induced air pouch model in rats Basic Protocol 6: Development and validation of reference articles in MSU-induced air pouch model in mice Support Protocol 2: Flow cytometry of mouse neutrophils in air pouch lavage samples.
痛风是一种由单水尿酸钠（MSU）晶体在体内沉积引起的慢性疾病，尤其是在一个或多个关节中沉积，这可能导致突然发作的严重疼痛、肿胀、发红和压痛，即痛风发作。痛风在历史上被称为“帝王病”，是最古老的关节疾病之一，至今仍是21世纪困扰人类的最常见的炎症性关节炎形式。它与心血管、代谢和肾脏合并症相关，可导致活动能力下降和身体功能受损，并导致旷工。鉴于其在全球范围内的发病率不断上升，迫切需要针对痛风性关节炎疾病的新疗法。实验性痛风模型是在临床前阶段阐明疾病发病机制以及评估新开发治疗方法的疗效和副作用的不可或缺的工具。在此，我们描述了一系列在啮齿动物和兔子中高度可重复的急性痛风发作和气袋模型，可用于解决与痛风发作期间及之后的病理变化和免疫反应相关的各种科学问题。由MSU晶体引发的动物痛风发作模型模拟了人类痛风性关节炎的主要组织病理学特征，包括软骨损伤和关节肿胀。同时，气袋模型可作为评估强大的炎症细胞因子分泌和中性粒细胞浸润的工具。本文详细描述了在动物中可重复诱导痛风发作和气袋模型所需的程序和故障排除技巧，并对该疾病的发病机制进行了批判性评估。©2025威利期刊有限责任公司。基本方案1：尿酸钠晶体的制备 基本方案2：MSU诱导的小鼠痛风发作模型的建立 支持方案1：小鼠踝关节组织的组织学评估 基本方案3：MSU诱导的大鼠痛风发作模型的建立 基本方案4：MSU诱导的兔子痛风发作模型的建立 基本方案5：MSU诱导的大鼠气袋模型中参考文献的开发与验证 基本方案6：MSU诱导的小鼠气袋模型中参考文献的开发与验证 支持方案2：气袋灌洗样本中小鼠中性粒细胞的流式细胞术
