Increased atherosclerosis in diabetic dyslipidemic swine: protection by atorvastatin involves decreased VLDL triglycerides but minimal effects on the lipoprotein profile
Increased atherosclerosis in diabetic dyslipidemic swine: protection by atorvastatin involves decreased VLDL triglycerides but minimal effects on the lipoprotein profile
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DOI：
10.1194/jlr.m200134-jlr200
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发表时间：
2002-10-01
影响因子：
6.5
通讯作者：
Sturek, M
中科院分区：
文献类型：
--
作者：
Dixon, JL;Shen, SM;Sturek, M
将雄性尤卡坦猪分为4组，每组5~6头猪：低脂对照组(3%)、高脂/2%胆固醇组(HF)、高脂/高胆固醇组、四氧嘧啶糖尿病组(DF)和阿托伐他汀(80 mg/d；DF+A组)。每天喂猪两餐，糖尿病猪每天注射胰岛素，以保持血糖在250至350 mg/dl之间。糖尿病高脂血症(DF)猪与正常血糖高脂血症猪相比，冠状动脉粥样硬化程度更重，乳内动脉胶原沉积增加。虽然总胆固醇和低密度脂蛋白胆固醇的浓度没有差异，但DF猪的甘油三酯(TG)水平升高，FPLC分析表明DF猪的LDL/HDLCH比率显著高于HF猪。DF猪的低密度脂蛋白部分含有更大的、富含脂肪的颗粒，类似于IDL。食用高脂肪/高胆固醇饮食导致血脂中14：0脂肪酸的百分比适度增加，这被几种不饱和脂肪酸的小幅-中度下降所抵消。与HF猪相比，DF猪的磷脂花生四烯酸含量显著增加。阿托伐他汀对糖尿病猪动脉粥样硬化有保护作用，降低总胆固醇和极低密度脂蛋白甘油三酯，但对FPLC脂蛋白和血浆脂肪酸组成以及血浆总胆固醇和低密度脂蛋白、维生素A、维生素E和溶血磷脂酰胆碱浓度影响不大。在所有组中，血浆CH浓度与肝脏CH浓度呈正相关。这些结果提示阿托伐他汀对糖尿病冠状动脉粥样硬化的保护作用可能与其对血浆VLDLTG浓度的影响有关。缺乏对其他脂质参数的主要影响，包括低密度脂蛋白/高密度脂蛋白比率，提示阿托伐他汀可能还有其他抗动脉粥样硬化的作用，可能直接在血管壁。
Male Yucatan swine were allocated to four groups (n = 5-6 pigs per group): low fat (3%) fed control, high fat/2% cholesterol (CH) fed (HF), high fat/CH fed,with alloxan-induced diabetes (DF) and DF pigs that were treated with atorvastatin (80 mg/day; DF+A). Pigs were fed two meals per day and daily insulin injections were used in diabetic pigs to maintain plasma glucose between 250 and 350 mg/dl. Diabetic dyslipidemic (DF) pigs exhibited greater coronary atherosclerosis and increased collagen deposition in internal mammary artery compared with normoglycemic hyperlipidemic pigs. Although total and LDL CH concentrations did not differ, triglyceride (TG) were increased in DF pigs and FPLC analysis indicated that the LDL/HDL CH ratio was significantly increased in DF compared with HF pigs. The LDL fraction of DF pigs contained larger, lipid enriched particles resembling IDL. Consumption of the high fat/CH diet caused a moderate increase in the percentage of 14:0 fatty acids in plasma lipids and this was compensated by small-moderate declines in several unsaturated fatty acids. There was a significant increase in phospholipid arachidonic acid in DF compared with HF pigs. Atorvastatin protected diabetic pigs from atherosclerosis and decreased total and VLDL TG, but exerted minimal effects on the FPLC lipoprotein and plasma fatty acid profiles and plasma concentrations of total and LDL CH, vitamin A, vitamin E, and lysophosphatidylcholine. Across all groups the plasma CH concentration was positively correlated with hepatic CH concentration. Ea These findings suggest that atorvastatin's protection against coronary artery atherosclerosis in diabetes may involve effects on plasma VLDL TG concentration. Lack of major effects on other lipid parameters, including the LDL/HDL ratio, suggests that atorvastatin may have yet other anti-atherogenic effects, possibly directly in the vessel wall.