Cannizzo Beatriz, Luján Agustín, Estrella Natalia, Lembo Carina, Cruzado Montserrat, Castro Claudia
Laboratory of Vascular Biology, Institute of Medicine and Experimental Biology of Cuyo (IMBECU)-CONICET, Faculty of Medical Sciences, National University of Cuyo, 5500 Mendoza, Argentina.
Exp Diabetes Res. 2012;2012:941304. doi: 10.1155/2012/941304. Epub 2012 Mar 7.
High fructose intake induces an insulin resistance state associated with metabolic syndrome (MS). The effect of vascular inflammation in this model is not completely addressed. The aim of this study was to evaluate vascular remodeling, inflammatory and oxidative stress markers, and atheroma development in high-fructose diet-induced insulin resistance of ApoE-deficient mice (ApoE-KO). Mice were fed with either a normal chow or a 10% w/v fructose (HF) in drinking water over a period of 8 weeks. Thereafter, plasma metabolic parameters, vascular remodeling, atheroma lesion size, inflammatory markers, and NAD(P)H oxidase activity in the arteries were determined. HF diet induced a marked increase in plasma glucose, insulin, and triglycerides in ApoE-KO mice, provoked vascular remodeling, enhanced expression of vascular cell-adhesion molecule-1 (VCAM-1) and matrix metalloprotease 9 (MMP-9) and enlarged atherosclerotic lesion in aortic and carotid arteries. NAD(P)H oxidase activity was enhanced by fructose intake, and this effect was attenuated by tempol, a superoxide dismutase mimetic, and losartan, an Angiotensin II receptor antagonist. Our study results show that high-fructose-induced insulin resistance promotes a proinflammatory and prooxidant state which accelerates atherosclerotic plaque formation in ApoE-KO mice.
高果糖摄入会引发与代谢综合征（MS）相关的胰岛素抵抗状态。在该模型中血管炎症的影响尚未得到充分研究。本研究的目的是评估高果糖饮食诱导的载脂蛋白E缺陷小鼠（ApoE-KO）胰岛素抵抗中的血管重塑、炎症和氧化应激标志物以及动脉粥样硬化的发展情况。将小鼠分为两组，一组喂食正常饲料，另一组在8周内饮用含10% w/v果糖（HF）的水。之后，测定血浆代谢参数、血管重塑、动脉粥样硬化病变大小、炎症标志物以及动脉中的NAD(P)H氧化酶活性。高果糖饮食导致ApoE-KO小鼠的血浆葡萄糖、胰岛素和甘油三酯显著升高，引发血管重塑，增强血管细胞黏附分子-1（VCAM-1）和基质金属蛋白酶9（MMP-9）的表达，并使主动脉和颈动脉中的动脉粥样硬化病变增大。果糖摄入增强了NAD(P)H氧化酶活性，而超氧化物歧化酶模拟物tempol和血管紧张素II受体拮抗剂氯沙坦可减弱这种作用。我们的研究结果表明，高果糖诱导的胰岛素抵抗促进了促炎和促氧化状态，加速了ApoE-KO小鼠动脉粥样硬化斑块的形成。
