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慢性病恶病质和肌肉减少症的动物模型:心脏功能、身体成分变化及治疗结果。

Animal models of cachexia and sarcopenia in chronic illness: Cardiac function, body composition changes and therapeutic results.

作者信息

Ishida Junichi, Saitoh Masakazu, Doehner Wolfram, von Haehling Stephan, Anker Markus, Anker Stefan D, Springer Jochen

机构信息

Institute of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.

Institute of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.

出版信息

Int J Cardiol. 2017 Jul 1;238:12-18. doi: 10.1016/j.ijcard.2017.03.154. Epub 2017 Apr 2.

Abstract

Cachexia is defined as a complex metabolic syndrome associated with underlying illness that is characterized by the loss of body weight consisting of muscle and fat mass wasting. Sarcopenia is defined as the ageing related loss of muscle mass in health and disease that may not have an effect on body weight. As millions of patients are in cachectic or sarcopenic states, both conditions contribute to high numbers to death worldwide. A number of treatments have been proposed for cachexia and sarcopenia, but these are either in the preclinical stage or in clinical trials and hence not available to the general population. Particularly in cachexia there is a massive problem of recruiting patients for trials and also with the follow-up, due to the seriousness of the disease. This underlines the importance of well-characterized animal models. Obviously, most of the widely used cachexia and sarcopenia animal models have limitations in reproducibility of the condition and novel models are warranted in this context. The key findings of developing models in the field of cachexia and sarcopenia are that more types of the conditions have been taken into the researchers' interest. In cardiac cachexia, technical issues, which limit the preciseness and reproducibility in surgical heart failure models, have been overcome by a combination of surgery and the use of transgenic mouse models or salt sensitive rat models. Fatigue is the most pronounced symptom of cachexia and may be caused by reduced cardiac function independent of the underlying disease. Sarcopenia models often suffer from the use of young animals, due to the limited availability and very high costs of using aged animals. This review will focus on rodent models designed to mimic cachexia and sarcopenia including co-morbidities such as cancer, heart failure, as well as other diseases and conditions.

摘要

恶病质被定义为一种与潜在疾病相关的复杂代谢综合征,其特征是体重减轻,包括肌肉和脂肪量的消耗。肌肉减少症被定义为在健康和疾病状态下与衰老相关的肌肉量减少,可能对体重没有影响。由于数百万患者处于恶病质或肌肉减少症状态,这两种情况在全球范围内导致了大量死亡。已经提出了一些针对恶病质和肌肉减少症的治疗方法,但这些方法要么处于临床前阶段,要么处于临床试验阶段,因此普通人群无法使用。特别是在恶病质方面,由于疾病的严重性,招募患者进行试验以及随访都存在巨大问题。这凸显了特征明确的动物模型的重要性。显然,大多数广泛使用的恶病质和肌肉减少症动物模型在该病症的可重复性方面存在局限性,因此在这种情况下需要新的模型。在恶病质和肌肉减少症领域开发模型的关键发现是,更多类型的病症已引起研究人员的关注。在心脏恶病质中,手术心力衰竭模型中限制精确性和可重复性的技术问题已通过手术与转基因小鼠模型或盐敏感大鼠模型的联合使用得以克服。疲劳是恶病质最明显的症状,可能由与潜在疾病无关的心脏功能降低引起。由于使用老龄动物的可用性有限且成本非常高,肌肉减少症模型通常使用年轻动物。本综述将重点关注旨在模拟恶病质和肌肉减少症的啮齿动物模型,包括合并症,如癌症、心力衰竭以及其他疾病和病症。

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