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用于代谢综合征、消化和骨骼疾病的猪模型:概述

Porcine models for the metabolic syndrome, digestive and bone disorders: a general overview.

作者信息

Litten-Brown J C, Corson A M, Clarke L

机构信息

Department of Agriculture, University of Reading, Earley Gate, PO Box 237, Reading, Berkshire, RG6 6AR, UK.

出版信息

Animal. 2010 Jun;4(6):899-920. doi: 10.1017/S1751731110000200.

Abstract

The aim of this review article is to provide an overview of the role of pigs as a biomedical model for humans. The usefulness and limitations of porcine models have been discussed in terms of metabolic, cardiovascular, digestive and bone diseases in humans. Domestic pigs and minipigs are the main categories of pigs used as biomedical models. One drawback of minipigs is that they are in short supply and expensive compared with domestic pigs, which in contrast cost more to house, feed and medicate. Different porcine breeds show different responses to the induction of specific diseases. For example, ossabaw minipigs provide a better model than Yucatan for the metabolic syndrome as they exhibit obesity, insulin resistance and hypertension, all of which are absent in the Yucatan. Similar metabolic/physiological differences exist between domestic breeds (e.g. Meishan v. Pietrain). The modern commercial (e.g. Large White) domestic pig has been the preferred model for developmental programming due to the 2- to 3-fold variation in body weight among littermates providing a natural form of foetal growth retardation not observed in ancient (e.g. Meishan) domestic breeds. Pigs have been increasingly used to study chronic ischaemia, therapeutic angiogenesis, hypertrophic cardiomyopathy and abdominal aortic aneurysm as their coronary anatomy and physiology are similar to humans. Type 1 and II diabetes can be induced in swine using dietary regimes and/or administration of streptozotocin. Pigs are a good and extensively used model for specific nutritional studies as their protein and lipid metabolism is comparable with humans, although pigs are not as sensitive to protein restriction as rodents. Neonatal and weanling pigs have been used to examine the pathophysiology and prevention/treatment of microbial-associated diseases and immune system disorders. A porcine model mimicking various degrees of prematurity in infants receiving total parenteral nutrition has been established to investigate gut development, amino acid metabolism and non-alcoholic fatty liver disease. Endoscopic therapeutic methods for upper gastrointestinal tract bleeding are being developed. Bone remodelling cycle in pigs is histologically more similar to humans than that of rats or mice, and is used to examine the relationship between menopause and osteoporosis. Work has also been conducted on dental implants in pigs to consider loading; however with caution as porcine bone remodels slightly faster than human bone. We conclude that pigs are a valuable translational model to bridge the gap between classical rodent models and humans in developing new therapies to aid human health.

摘要

这篇综述文章的目的是概述猪作为人类生物医学模型的作用。已从人类的代谢、心血管、消化和骨骼疾病方面讨论了猪模型的实用性和局限性。家猪和小型猪是用作生物医学模型的主要猪种。小型猪的一个缺点是与家猪相比,它们供应短缺且价格昂贵,而家猪在饲养、喂食和用药方面成本更高。不同的猪品种对特定疾病的诱导表现出不同的反应。例如,奥萨巴小型猪比尤卡坦猪更适合作为代谢综合征的模型,因为它们表现出肥胖、胰岛素抵抗和高血压,而尤卡坦猪则没有这些症状。家猪品种之间(如梅山猪与皮特兰猪)也存在类似的代谢/生理差异。现代商业家猪(如大白猪)一直是发育编程的首选模型,因为同窝仔猪体重有2至3倍的差异,提供了一种古代家猪品种(如梅山猪)未观察到的自然形式的胎儿生长受限。由于猪的冠状动脉解剖结构和生理机能与人类相似,猪越来越多地被用于研究慢性缺血、治疗性血管生成、肥厚性心肌病和腹主动脉瘤。使用饮食方案和/或注射链脲佐菌素可在猪身上诱发1型和2型糖尿病。猪是特定营养研究的良好且广泛使用的模型,因为它们的蛋白质和脂质代谢与人类相当,尽管猪对蛋白质限制的敏感性不如啮齿动物。新生猪和断奶仔猪已被用于研究微生物相关疾病和免疫系统疾病的病理生理学及预防/治疗。已建立了一个模拟接受全胃肠外营养的婴儿不同程度早产的猪模型,以研究肠道发育、氨基酸代谢和非酒精性脂肪肝病。正在开发上消化道出血的内镜治疗方法。猪的骨重塑周期在组织学上比大鼠或小鼠更类似于人类,可用于研究绝经与骨质疏松症之间的关系。也已对猪的牙种植体进行了加载方面的研究;不过要谨慎,因为猪骨重塑比人类骨骼略快。我们得出结论,在开发有助于人类健康的新疗法方面,猪是一种有价值的转化模型,可弥合经典啮齿动物模型与人类之间的差距。

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