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将斑马鱼作为人类肥胖相关性肾小球病的模型。

Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy.

机构信息

Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

出版信息

Biochem Biophys Res Commun. 2013 Feb 22;431(4):712-7. doi: 10.1016/j.bbrc.2013.01.053. Epub 2013 Jan 23.

Abstract

Obesity, an ongoing significant public health problem, is a part of complex disease characterized as metabolic syndrome. Medaka and zebrafish are useful aquatic experimental animals widely used in the field of toxicology and environmental health sciences and as a human disease models. In medaka, simple feeding of a high fat diet (HFD) can induce body weight gain, excessive accumulation of visceral adipose tissue, hyperglycemia, hyperlipidemia, and steatohepatitis, which mimics human metabolic syndrome. In the present study, to explore the possibility that the adult medaka fed with HFD (HFD-medaka) can be used as an animal model for human metabolic syndrome-associated glomerular disease, including obesity-related glomerulopathy (ORG), we analyzed structural alterations and protein expression in the mesonephric kidney of HFD-medaka. We found that the histopathology was consistent with glomerulomegaly accompanied by the dilation of glomerular capillaries and proliferative expansion of the mesangium, a condition partially comparable to human ORG. Moreover, expressions of several kinds of kidney disease-related proteins (such as MYH9, SM22α) were significantly elevated. Thus, the HFD-medaka has a high potential as an animal model useful for exploring the mechanism underling human ORG.

摘要

肥胖是一个持续存在的重大公共卫生问题,是代谢综合征等复杂疾病的一部分。斑马鱼和牙鲆是广泛应用于毒理学和环境卫生科学领域的水生实验动物,也是人类疾病模型。在牙鲆中,简单地投喂高脂肪饮食(HFD)可导致体重增加、内脏脂肪组织过度积累、高血糖、高血脂和脂肪性肝炎,模拟人类代谢综合征。在本研究中,为了探索用高脂肪饮食喂养的成年牙鲆(HFD-牙鲆)是否可作为人类代谢综合征相关肾小球疾病(包括肥胖相关肾小球病(ORG))的动物模型,我们分析了 HFD-牙鲆中中肾的结构改变和蛋白质表达。我们发现,组织病理学与肾小球肥大一致,伴有肾小球毛细血管扩张和系膜增殖性扩张,与人类 ORG 部分相似。此外,几种肾脏疾病相关蛋白(如 MYH9、SM22α)的表达显著升高。因此,HFD-牙鲆作为一种有用的动物模型,具有探索人类 ORG 发病机制的巨大潜力。

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