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心脏代谢综合征:现有小鼠模型的更新。

Cardiometabolic Syndrome: An Update on Available Mouse Models.

机构信息

Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

出版信息

Thromb Haemost. 2021 Jun;121(6):703-715. doi: 10.1055/s-0040-1721388. Epub 2020 Dec 6.

Abstract

Cardiometabolic syndrome (CMS), a disease entity characterized by abdominal obesity, insulin resistance (IR), hypertension, and hyperlipidemia, is a global epidemic with approximately 25% prevalence in adults globally. CMS is associated with increased risk for cardiovascular disease (CVD) and development of diabetes. Due to its multifactorial etiology, the development of several animal models to simulate CMS has contributed significantly to the elucidation of the disease pathophysiology and the design of therapies. In this review we aimed to present the most common mouse models used in the research of CMS. We found that CMS can be induced either by genetic manipulation, leading to dyslipidemia, lipodystrophy, obesity and IR, or obesity and hypertension, or by administration of specific diets and drugs. In the last decade, the and mice were the most common obesity and IR models, whereas and were widely used to induce hyperlipidemia. These mice have been used either as a single transgenic or combined with a different background with or without diet treatment. High-fat diet with modifications is the preferred protocol, generally leading to increased body weight, hyperlipidemia, and IR. A plethora of genetically engineered mouse models, diets, drugs, or synthetic compounds that are available have advanced the understanding of CMS. However, each researcher should carefully select the most appropriate model and validate its consistency. It is important to consider the differences between strains of the same animal species, different animals, and most importantly differences to human when translating results.

摘要

代谢综合征(CMS)是一种以腹部肥胖、胰岛素抵抗(IR)、高血压和高血脂为特征的疾病实体,是一种全球性流行疾病,在全球成年人中的患病率约为 25%。CMS 与心血管疾病(CVD)风险增加和糖尿病的发展有关。由于其多因素病因,已经开发出几种模拟 CMS 的动物模型,这对阐明疾病病理生理学和设计治疗方法做出了重要贡献。在这篇综述中,我们旨在介绍 CMS 研究中最常用的小鼠模型。我们发现,CMS 可以通过遗传操作诱导,导致血脂异常、脂肪营养不良、肥胖和 IR,或者通过特定饮食和药物的给药来诱导肥胖和高血压。在过去十年中, 和 小鼠是最常见的肥胖和 IR 模型,而 和 被广泛用于诱导高血脂。这些小鼠要么作为单一转基因,要么与不同背景结合使用,无论是饮食治疗还是不治疗。经过改良的高脂肪饮食是首选方案,通常会导致体重增加、高血脂和 IR。大量的基因工程小鼠模型、饮食、药物或合成化合物的可用性提高了对 CMS 的认识。然而,每个研究人员都应该仔细选择最合适的模型,并验证其一致性。在将结果转化为人类时,需要考虑同一动物物种、不同动物之间的差异,最重要的是与人类之间的差异。

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