Dyslipidemia and vascular dysfunction in diabetic pigs fed an atherogenic diet
Dyslipidemia and vascular dysfunction in diabetic pigs fed an atherogenic diet
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DOI：
10.1161/01.atv.19.12.2981
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发表时间：
1999-12-01
影响因子：
8.7
通讯作者：
Sturek, M
中科院分区：
文献类型：
--
作者：
Dixon, JL;Stoops, JD;Sturek, M
糖尿病患者通常不仅患有高血糖，还患有血脂异常。不完善的动物模型阻碍了糖尿病环境致病成分和加速动脉粥样硬化机制的研究。猪是一种可能适合人类糖尿病血脂异常的动物模型，因为它与人类相似，携带很大一部分低密度脂蛋白（LDL）总胆固醇。在这项研究中，雄性辛克莱小型猪通过用四氧嘧啶破坏胰腺中产生胰岛素的细胞而患上糖尿病，然后饲喂高脂肪和高胆固醇饮食，以与饲喂非糖尿病高脂肪和高胆固醇饮食的猪和对照猪进行比较。糖尿病猪表现出高血糖，但血浆尿素氮、肌酐和转氨酶水平在正常范围内，表明对肾和肝功能没有不利影响。糖尿病猪的脂蛋白谱与人类糖尿病患者的脂蛋白谱相似，其特点是高甘油三酯血症（与对照猪和高脂饲喂猪相比增加了 2.8 倍），与高脂饲喂猪（64%）和对照猪（57%）相比，胆固醇分布显着转变为 LDL 部分（81%），糖尿病猪中 LDL 颗粒富含脂质且更加异质，载脂蛋白 B 分布范围更广在糖尿病猪中，LDL颗粒和载脂蛋白E部分从高密度脂蛋白重新分配为含载脂蛋白B的脂蛋白。载脂蛋白A-I分布几乎没有变化。糖尿病猪表现出多种血管疾病的早期迹象。在糖尿病猪中，75% 的冠状动脉节段对前列腺素 F-2 α 响应出现收缩振荡，而高脂喂养猪中为 25%，对照猪为 10%，糖尿病猪中内皮依赖性肱动脉松弛几乎被消除，但与对照猪相比，高脂喂养猪中没有变化，颈动脉苏丹 IV 染色仅在糖尿病猪中脂肪条纹显着增加，该猪模型应深入了解人类糖尿病血脂异常的病因，并促进糖尿病患者外周血管和冠状动脉疾病的研究。
Diabetic patients typically have not only hyperglycemia but also dyslipidemia. Study of the pathogenic components of the diabetic milieu and mechanisms of accelerated atherosclerosis is hindered by inadequate animal models. A potentially suitable animal model for human diabetic dyslipidemia is the pig, because it carries a large fraction of total cholesterol in low-density lipoprotein (LDL), similar to humans. In this study, male Sinclair miniature pigs were made diabetic by destroying the insulin-producing cells of the pancreas with alloxan and then were fed a high fat and high cholesterol diet for comparison with pigs fed a nondiabetic high fat and high cholesterol diet and control pigs. Diabetic pigs exhibited hyperglycemia, but plasma urea nitrogen, creatinine, and transaminase levels were in the normal range, indicating no adverse effects on kidney and liver function. The lipoprotein profile in diabetic pigs was similar to that found in human diabetic patients and was characterized by hypertriglyceridemia (2.8-fold increase versus control and high fat-fed pigs) and a profound shift of cholesterol distribution into the LDL fraction (81%) versus the distribution in high fat-fed (64%) and control (57%) pigs, LDL particles were lipid-enriched and more heterogeneous in diabetic pigs, Apolipoprotein B was distributed among a much broader spectrum of LDL particles, and apolipoprotein E was partially redistributed from high-density lipoprotein to apolipoprotein B-containing lipoproteins in diabetic pigs. There was little change in apolipoprotein A-I distribution. Diabetic pigs showed several early signs of excess vascular disease. In diabetic pigs, 75% of the coronary artery segments showed contractile oscillations in response to prostaglandin F-2 alpha compared with 25% in high fat-fed pigs and 10% in control pigs, Endothelium-dependent relaxation of brachial arteries was nearly abolished in diabetic pigs but unchanged in high fat-fed versus control pigs, Carotid artery Sudan IV staining for fatty streaks was significantly increased only in diabetic pigs, This porcine model should provide insights into the etiology of human diabetic dyslipidemia and facilitate study of peripheral vascular and coronary artery disease in diabetic patients.