大鼠血管内皮功能障碍及胰岛素抵抗与高脂饮食的关系

Relationship of vascular endothelial dysfunction and insulin resistance with high-fat diet in rats

目的:观察高脂饮食大鼠胰岛素抵抗的发生以及血管内皮功能的变化。方法:实验于2006-05/06在东南大学实验动物中心完成。选用健康SD雄性大鼠16只,体质量150～180g,随机数字表法分为正常对照组和高脂饮食组,每组8只。正常对照组用普通饲料(成分:米糠80g,玉米粉500g,黄豆粉300g,骨粉30g,维生素13g,矿物质67g)喂养,高脂饮食组用高脂饲料(葵花油325g,玉米粉254g,全脂奶粉230g,米糠51g,鸡蛋30g,维生素13g,矿物质67g,骨粉30g,混合制成1000g)喂养4周。观察高脂饮食对大鼠空腹血糖、空腹胰岛素、胰岛素敏感指数、胰岛素抵抗指数、口服葡萄糖耐量试验、体质量、血浆内皮素1和血清一氧化氮的影响,以免疫组织化学方法检测血管内皮细胞内皮素1、内皮型一氧化氮合酶蛋白的表达。结果:纳入大鼠16只均进入结果分析。①4周后高脂饮食组大鼠空腹胰岛素、胰岛素抵抗指数、体质量、血浆内皮素1及血管内皮细胞内皮素1阳性细胞数均明显高于正常对照组[(27.50±2.15),(14.30±1.89)mIU/L,P<0.01;(6.60±1.26),(3.28±0.57),P<0.01;(332.69±15.85),(312.38±16.37)g,P<0.05;(77.82±6.28),(64.72±5.42)ng/L,P<0.01;(47.50±2.51),(32.47±3.44),P<0.01]。②高脂饮食组大鼠胰岛素敏感指数、血清一氧化氮及血管内皮型一氧化氮合酶阳性细胞数均明显低于正常对照组[(-4.99±0.17),(-4.29±0.19);(46.50±3.08),(54.63±5.58)μmol/L;(48.17±3.55),(55.50±3.15),P<0.01]。③4周后口服葡萄糖耐量试验高脂饮食组在30,60,120min血糖值均高于正常对照组,差异有显著性意义[(8.71±0.63),(7.90±0.53)mmol/L,P<0.05;(9.51±0.45),(7.28±0.43)mmol/L,P<0.01;(6.58±0.48),(5.80±0.58)mmol/L,P<0.05)。结论:高脂饮食可致大鼠胰岛素抵抗和血管内皮功能障碍,血脂代谢障碍是促成胰岛素抵抗的形成和血管内皮功能障碍的主要危险因素之一。

AIM： To observe the effect of high-fat diet on experimental rats of insulin resistance and vascular endothelial function. METHODS： The experiment was conducted in the Central Laboratory for Animals, Southeast University from May to June in 2006. Sixteen male SD rats （150-180 g） were randomly divided into two groups： control group and high-fat diet group with 8 rats in each. Insulin resistance was induced in rats by feeding high-fat diet （1 000 g mixture included sunflower oil 325 g, corn flour 254 g, dried whole milk 230 g, rice bran 51 g, eggs 30 g, vitamin 13 g, mineral matter 67 g, bone meal 30 g） while the control rats were fed with normal pellet diet （rice bran 80 g, corn flour 500 g, soybean flour 300 g, bone meal 30 g, vitamin 13 g, mineral matter 67 g） for a period of 4 weeks. The effects of high-fat diet on fasting blood glucose （FBG）, fasting insulin （FINS）, insulin sensitivity index （ISI）, HOMA insulin resistance index （HOMA-IRI）, oral glucose tolerance test （OGTT）, body weigh, plasma endothelin （ET）-I and serum nitrogen monoxidum （NO） were observed. The protein of ET-1 and endothelial nitric oxide synthase （eNOS） in vascular endothelial cells was assayed by immunohistochemistry. RESULTS： A total of 16 rats were involved in the analysis of results, no rat died in the experiment. （1）After 4 weeks, FINS, HOMA-IRI, body weigh, plasma ET-1 and the protein of and ET-1 in vascular endothelial cell of rats in the high-fat diet group were obviously higher than those in the control group [（27.50±2.15）, （14.30±1.89） mlU/L, P 〈 0,01; （6.60± 1.26）, （3.28±0.57）, P〈 0.01; （332.69±15.85）, （312.38±16.37）g, P〈 0.05; （77.82±6.28）, （64.72±5.42） ng/L, P〈 0.01; （47.50±2.51）, （32.47±3.44）, P 〈 0.01].（2）While the ISl, serum NO and the protein of and eNOS in vascular endothelial cell of rats in the high-fat diet group were significantly lower than those in the control group [（-4.99±0.17）, （-4.29±0.19）; （46.50±3.08）, （54.63±5.58） p.mol/L; （48.17±3.55）, （55.50±3.15）, P〈 0.01].±）After 4 weeks, the blood glucose of OGTT at 30, 60, 120 minutes in the high-fat diet group were also higher than those in the control group [（8.71±0.63）, （7.90± 0.53） mmol/L, P〈 0.05; （9.51±0.45）, （7.28±0.43） mmol/L, P〈 0.01; （6.58±0.48）, （5.80±0.58） mmol/L, P〈 0.05]. CONCLUSION：Insulin resistance and vascular endothelial dysfunction of experimental rats may be induced by high-fat feedin dyslipidemia is one of the main risk factors for the formation of insulin resistance and vascular endothelial dysfunction.