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gANT对高脂大鼠内皮功能的影响及其分子机制

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第3期
页码:
318-321，331
栏目:
基础研究
出版日期:
2010-04-06

文章信息/Info

Title:
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
第四军医大学：1.西京医院老年病科，2.生理学教研室，陕西 西安 710032
Author(s):
LI Rong1;  WANG Wen-qing1;  ZHANG Hai-feng2;  XU Ming2;  WANG Xiao-ming1
1.Department of Geriatrics, Xijing Hospital, 2.Department of Physiology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
脂联素; 高脂血症; 血管内皮功能; 一氧化氮; 大鼠
Keywords:
adiponectin;  hyperlipidemia;  endothelial function;  nitric oxide;  rat
分类号:
R589.2
DOI:
-
文献标识码:
A
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。
Abstract:
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 bioactive NO production and preserving its bioactivity.

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备注/Memo

备注/Memo:
收稿日期：2009-11-27.基金项目：国家自然科学基金资助项目（30700308） 通讯作者：王晓明，主任医师，主要从事代谢综合征发病机制及防治的研究Email:xmwang@fmmu.edu.cn 作者简介：李榕，主治医师，博士Email:rongli.li09@gmail.com
更新日期/Last Update: 2010-04-09