Aleixandre de Artiñano Amaya, Miguel Castro Marta
Department of Pharmacology, Faculty of Medicine, Complutense University, Madrid, Spain.
Br J Nutr. 2009 Nov;102(9):1246-53. doi: 10.1017/S0007114509990729. Epub 2009 Jul 27.
Being the metabolic syndrome a multifactorial condition, it is difficult to find adequate experimental models to study this pathology. The obese Zucker rats, which are homozygous for the fa allele, present abnormalities similar to those seen in human metabolic syndrome and are a widely extended model of insulin resistance. The usefulness of these rats as a model of non-insulin-dependent diabetes mellitus is nevertheless questionable, and they neither can be considered a clear experimental model of hypertension. Some experimental models different from the obese Zucker rats have also been used to study the metabolic syndrome. Some derive from the spontaneously hypertensive rats (SHR). In this context, the most important are the obese SHR, usually named Koletsky rats. Hyperinsulinism, associated with either normal or slightly elevated levels of blood glucose, is present in these animals, but SHR/N-corpulent rats are a more appropriated model of non-insulin-dependent diabetes mellitus. The SHR/NDmc corpulent rats, a subline of SHR/N-corpulent rats, also exhibit metabolic and histopathologic characteristics associated with human metabolic disorders. A new animal model of the metabolic syndrome, stroke-prone-SHR (SHRSP) fatty rats, was obtained by introducing a segment of the mutant leptin receptor gene from the Zucker line heterozygous for the fa gene mutation into the genetic background of the SHRSP. Very recently, it has been developed as a non-obese rat model with hypertension, fatty liver and characteristics of the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein in the SHR rats. The Wistar Ottawa Karlsburg W rats are also a new strain that develops a nearly complete metabolic syndrome. Moreover, a new experimental model of low-capacity runner rats has also been developed with elevated blood pressure levels together with the other hallmarks of the metabolic syndrome.
由于代谢综合征是一种多因素疾病，很难找到合适的实验模型来研究这种病理状况。肥胖的Zucker大鼠为fa等位基因的纯合子，表现出与人类代谢综合征相似的异常，是广泛应用的胰岛素抵抗模型。然而，这些大鼠作为非胰岛素依赖型糖尿病模型的实用性值得怀疑，它们也不能被视为明确的高血压实验模型。一些不同于肥胖Zucker大鼠的实验模型也被用于研究代谢综合征。有些源自自发性高血压大鼠（SHR）。在这种情况下，最重要的是肥胖SHR，通常称为科列茨基大鼠。这些动物存在高胰岛素血症，血糖水平正常或略有升高，但SHR/N肥胖大鼠是更合适的非胰岛素依赖型糖尿病模型。SHR/NDmc肥胖大鼠是SHR/N肥胖大鼠的一个亚系，也表现出与人类代谢紊乱相关的代谢和组织病理学特征。一种新的代谢综合征动物模型，即易中风的SHR（SHRSP）肥胖大鼠，是通过将来自fa基因突变杂合的Zucker系的一段突变瘦素受体基因导入SHRSP的遗传背景中获得的。最近，通过在SHR大鼠中转基因过表达固醇调节元件结合蛋白，已将其开发为一种具有高血压、脂肪肝和代谢综合征特征的非肥胖大鼠模型。Wistar Ottawa Karlsburg W大鼠也是一种新的品系，会发展出几乎完整的代谢综合征。此外，还开发了一种新的低耐力跑步大鼠实验模型，其血压升高，同时伴有代谢综合征的其他特征。
