gANT对高脂大鼠内皮功能的影响及其分子机制  

Molecular mechanism and effect of globular adiponectin on endothelial function in hyperlipidemic rats

作　　者：李榕[1] 王文清[1] 张海锋[2] 徐明[2] 王晓明[1] 

机构地区：[1]第四军医大学西京医院老年病科,陕西西安710032 [2]第四军医大学生理学教研室,陕西西安710032

出　　处：《心脏杂志》2010年第3期318-321,331,共5页Chinese Heart Journal

基　　金：国家自然科学基金资助项目(30700308)

摘　　要：目的:观察球状脂联素(gANT)对高脂血症大鼠血管内皮功能的影响,并探讨其主要信号转导机制。方法:选14只8周龄雄性SD大鼠分为对照组及高脂血症组(每组7只),分别以普通和高脂饲料喂养14周后,麻醉采血,用生化分析仪检测血清胆固醇和三酰甘油的水平,用ELISA法检测血浆脂联素(ANT)的水平。分离大鼠主动脉,与gANT共孵育,观察gANT对血管内皮功能、血管超氧化物生成量以及一氧化氮合酶(NOS)表达水平的影响。结果:与对照组比较,高脂血症组大鼠血浆胆固醇、三酰甘油及ANT的水平显著升高(P<0.01;P<0.05;P<0.05);血管内皮功能明显失调[乙酰胆碱引起的血管最大舒张率显著降低:(70.3±3.3)%vs.(95.2±2.5)%,P<0.01];血管组织中超氧化物生成显著增多(P<0.01);磷酸化内皮型NOS(p-eNOS)的表达降低(P<0.05),诱导型NOS(iNOS)的表达明显增加(P<0.01)。gANT可显著改善高脂血症组大鼠血管对ACh的舒张反应(P<0.01),降低超氧化物生成(P<0.01),上调p-eNOS表达(P<0.05)及抑制iNOS过表达(P<0.05)。结论:gANT可显著改善高脂血症组大鼠血管内皮功能,其机制与促进具有血管保护作用的一氧化氮(NO)的生成有关,也与其减少NO破坏有关。AIM： To observe the effects of globular adiponectin （gANT） on endothelial dysfunction in hyperlipidemic rats and to investigate the mechanisms involved. METHODS： Male Sprague Dawley rats aged 8 weeks were randomly fed with a regular or high-fat diet for 14 weeks. Caval blood was drawn to measure the lipid profile and ANT levels. Aorta was isolated and incubated with gANT. The influences of gANT on the vasorelaxation response to acetylcholine （ACh）, superoxide production and expression of p-eNOS and iNOS were determined. RESULTS： Compared with rats fed with a normal diet, animals fed a high-fat exhibited significantly increased cholesterol, triglyceride and ANT concentrations （P 〈 0. 01, P 〈 0. 05, P 〈 0. 05, respectively） , endothelium dysfunction [ percentage of maximum vasorelaxation ： （70.3 ±3.3）% vs. （95.2 ±2.5）%, P 〈0.01], increased superoxide production （P 〈0.01） and reversed expression of nitric oxide synthase in vessel tissue. Treatment with gANT significantly improved the vasorelaxation response to ACh （ P 〈 0. 01 ）, attenuated overproduction of superoxide （ P 〈 0.01 ）, increased eNOS phosphorylation （ P 〈 0. 05 ） and reduced iNOS levels （ P 〈 0.01 ） in hyperlipidemic vascular segments. CONCLUSION： gANT improves endothelial dysfunction by enhancing bioaetive NO production and preserving its bioactivity.

关 键 词：脂联素 高脂血症 血管内皮功能 一氧化氮 大鼠 

分 类 号：R589.2[医药卫生—内分泌]