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豚鼠模型将健康与疾病起源假说的发育翻译转化为临床实践。

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic.

机构信息

Early Origins of Adult Health Research Group, School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.

出版信息

J Physiol. 2018 Dec;596(23):5535-5569. doi: 10.1113/JP274948. Epub 2018 May 30.

Abstract

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig's potential to enhance clinical therapeutic innovation to improve human health.

摘要

30 多年前,大卫·巴克教授首次提出了这样一种理论,即生命早期的事件可以解释个体在以后生活中非传染性疾病的风险:健康与疾病的发育起源(DOHaD)假说。20 世纪 90 年代,大量的人类群体对 DOHaD 假说的有效性进行了广泛的检验,并在一系列实验动物模型中对其潜在机制进行了描述。在过去的十年中,研究人员一直试图利用 DOHaD 的这种机制理解,在妊娠和生命早期开发治疗干预措施,以改善成人健康。已经使用了多种动物模型来开发和评估干预措施,每种模型都有其优点和局限性。很明显,有效的转化研究需要选择尽可能接近人类胎儿生长和发育速度的动物模型,以便能够充分评估围产期损伤和/或治疗干预的效果。豚鼠就是这样一种动物模型,在过去的二十年中,它已经被证明是这些重要生殖研究的一个非常有用的平台。这篇综述强调了人类和豚鼠在子宫内发育方面的相似之处、豚鼠作为 DOHaD 实验模型的优势和局限性,以及豚鼠在提高临床治疗创新以改善人类健康方面的潜力。

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