ox-LDL/LOX-1与高脂肥胖幼鼠血管内皮功能障碍的相关性及烟酸的干预效果  

Relationship of ox-LDL/LOX-1 and vascular endothelial dysfunction of diet-induced obese immature rats and nicotinic acid＇s intervention outcomes

作　　者：牛娜[1] 孙书珍[1] 韩波[1] 汪翼[1] 

机构地区：[1]山东大学附属省立医院儿科,济南250021

出　　处：《中华医学杂志》2013年第42期3388-3393,共6页National Medical Journal of China

基　　金：山东省自然科学基金（ZR2011HM029）;山东省优秀中青年科学家科研奖励基金（BS2010YY056）

摘　　要：目的 探讨氧化低密度脂蛋白（ox-LDL）/ox-LDL受体1 （LOX-1）系统与高脂肥胖幼鼠血管内皮功能障碍的相关性和烟酸的干预效果及其可能机制.方法 21日龄断乳雄性Wistar大鼠30只,通过高脂饮食建立幼鼠高脂肥胖模型,设对照组、高脂组、烟酸组,各10只,于12周检测外周血血脂、ox-LDL、可溶性细胞间黏附分子（sICAM）-1水平,血浆内皮素,血清一氧化氮（NO）,主动脉血管壁 LOX-1、ICAM-1的基因和蛋白表达,主动脉ICAM-1、LOX-1蛋白的定位表达.结果 高脂组和烟酸组外周血甘油三酯、总胆固醇、LDH、ox-LDL、内皮素水平均高于对照组[（0.98±0.12） 和（0.69±0.06）比（0.49±0.06） mmol/L、（2.11±0.16）和（1.62±0.12）比（1.30±0.12） mmol/L、（0.71±0.04）和（0.50±0.03）比（0.30±0.04） mmol/L、（44.2±5.1）和（33.7±2.1）比（26.6±2.9） μg/L、（187±10）和（157±6）比（118±7） pg/ml],高脂组各指标均高于烟酸组（均P〈0.01）;高密度脂蛋白（HDL）和NO水平高脂组和烟酸组则均低于对照组 （均P〈0.01）,高脂组均低于烟酸组（均P〈0.01）;高脂组血管壁LOX-1、ICAM-1蛋白及mRNA的表达均高于对照组和烟酸组（均P〈0.01）.相关分析显示,ox-LDL与LOX-1、总胆固醇、甘油三酯、LDL、内皮素、ICAM-1显著正相关（r=0.918、0.867、0.857、0.834、0.869、0.644,均P〈0.01）,而与NO、HDL显著负相关（r=-0.823、-0.872,P〈0.01）.结论 烟酸早期应用可能通过调节血脂、干预血管ox-LDL和LOX-1的表达,发挥对饮食诱导的高脂肥胖幼鼠保护内皮功能的作用.Objective To explore the effects of nicotinic acid intervention on vascular endothelial dysfunction mediated by oxidized low density lipoprotein （ox-LDL）/lectin-like oxidized low density lipoprotein receptor-1 （LOX-1） in diet-induced obese immature rats and its possible mechanism through detecting the expression levels of ox-LDL and LOX-1 in abdominal arota. Methods A model of diet-induced obese immature rats was established by high-fat diet. And 30 immature rats were divided randomly and equally into control （n = 10）, high-fat （n = 10） and drug control （n = 10） groups. At the end of 12 weeks, the levels of serum total cholesterol （TC）, triglyceride （TG）, LDL and high-density lipoprotein （HDL） were examined. The levels of ox-LDL, soluble intercellular adhesion molecule-1 （sICAM-1）, endothelin and nitric oxide （NO） were detected. The gene and protein expressions of LOX-1 and ICAM-1 in abdominal aorta were detected. And the location protein expressions of LOX-1 and ICAM-1 were examined. Results High-fat diet induced hyperlipidemia and obesity in immature rats. The serum levels of TG, TC, LDL, ox-LDL and endothelin in high-fat and drug control groups were all higher than control group （ （ 0. 98 ± 0. 12 ） and （0. 69 ±0. 06） vs（0. 49 ±0. 06） mmol/L, （2. 11 ±0. 16） and （ 1.62 ±0. 12） vs （1.30 ±0. 12） mmol/L, （0.71±0.04） and （0.50 ±0.03） vs（0.30_±0.04） mmol/L, （44.2 ±5.1） and （33.7 ±2.1） vs （26. 6 ±2. 9） μg/L, （ 187 ± 10） and （ 157 ± 6） vs（ 118 ± 7） pg/ml）. The indices in high-fat group were higher than those in drug control group （ all P 〈 0. 01 ）. The levels of HDL and NO in high-fat and drug control groups were lower than those in control group（ all P 〈0. 01 ） ; the levels of HDL and NO in high-fat group lower than those in drug control group （ all P 〈 0. 01 ）. And the levels of LOX-1, ICAM-1 protein and mRNA in high-fat group were higher than those in drug control and control grou

关 键 词：内皮 受体 LDL 脂蛋白类 LDL 烟酸类 

分 类 号：R589.2[医药卫生—内分泌]