早期雌激素替代治疗对兔血管内皮衰老的影响及机制  

Effects of early estrogen replacement therapy on vascular endothelial senescence and its mechanism in rabbits

作　　者：李向平[1] 廖清池[1] 刘玲[1] 赵水平[1] 连亚军[1] 董海云[1] 

机构地区：[1]湖南长沙中南大学湘雅二医院心内科,410011

出　　处：《中华老年医学杂志》2009年第5期421-425,共5页Chinese Journal of Geriatrics

基　　金：国家自然科学基金资助项目（30500209）;湖南省科技厅资助项目（03SSY3080）

摘　　要：目的探讨早期不同剂量雌激素替代治疗（ERT）对去卵巢高脂血症雌兔主动脉内皮衰老的影响及可能机制。方法28只健康新西兰雌性白兔随机分为4组（每组7只）：假手术组行假手术；去卵巢组行双侧卵巢切除；小剂量ERT组行双侧卵巢切除加小剂量ERT（苯甲酸雌二醇200μg，隔日肌肉注射1次）；大剂量ERT组行双侧卵巢切除加大ERT剂量（苯甲酸雌二醇1000μg，隔日肌肉注射1次）。各组兔于术后1周开始给予高脂饲料喂养，小剂量ERT组和大剂量ERT组同时给予ERT。分别于术前、高脂喂食4周及12周后抽取耳中央动脉血，测定血清雌二醇、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白-胆固醇（LDL-C）、高密度脂蛋白-胆固醇（HDL-C）及非对称性二甲基精氨酸（ADMA）水平。实验结束时，分离兔主动脉行组织病理学分析并计算衰老血管内皮和动脉粥样硬化斑块面积。结果（1）12周后去卵巢组血清TC及LDL—C高于其他组（P〈0．01），而TG及HDL—C水平低于其他3组（P〈0．01）；小剂量和大剂量ERT组TC及LDL—C低于假手术组（P〈0．05），但TG及HDL—C与假手术组比较，差异无统计学意义（均P〉0．05）。（2）高脂喂食12周后各组兔血清ADMA水平均明显增高，小剂量和大剂量ERT组低于假手术组（P〈0．05）。（3）直线相关分析显示，主动脉粥样斑块面积与衰老内皮面积呈正相关（r=0．962，P〈0．01），两者均与血清TC、LDL—C和ADMA浓度呈正相关（r值分别为0．812、0．824、0．755、0．797、0．749、0．727，P〈0．01），与血清雌二醇呈显著负相关（r=-0．762和0．743，P〈0．01）。结论早期ERT可以改善血脂代谢、降低ADMA水平、减轻血管内皮衰老及动脉粥样硬化斑块形成，雌激素延缓内皮衰老的作用可能与改善血脂代谢、降低ADMA水平有关。Objective To investigate the effects of early estrogen replacement therapy（ERT） with different doses on aortic endothelial senescence and its possible mechanism. Methods Twentyeight healthy New Zealand white female rabbits were randomized into four groups： group A（n= 7）, in sham operation; group B（n= 7）, ovariectomized; group C（n=7）, ovaricctomized and in low dose ERT（cstradiol benzoate 200μg,im,QOD） ; and group D（n=7）, ovariectomized and in high-dose ERT （estradiol benzoate 1000 μg,im,QOD）. All rabbits were fed with high fat diet and the rabbits in group C and group D were given ERT from the 7th day after the operation. Blood samples taken via ear central artery before the operation and after the high fat diet for 4 and 12 weeks were used to determine the concentrations of serum estradiol（E2 ）, total cholestcrol（TC）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, triglyceride （TG） and asymmetric dimethylarginine（ADMA）. After 12 weeks, the aorta was separated for histopathologic analysis and the areas of senescent endothelium and atherosclerotic plaque were calculated. Results （1） After ovariectomized, the concentration of serum estradiol（E2 ） was significantly lower in group B than in other groups （all P〈0.05）. Twelve weeks later, the level of E2 in was higher group D than in group A and C（both P〈0.05）, but there was no significant difference between group C and group A （P〈0.05）. （2）After the high fat diet for 4 and 12 weeks, there was a notable increase of TC, LDL C, TG and HDL-C levels in rabbits of each group（all P〈0.01）. After 12 weeks, the levels of TC and LDL- C were remarkably higher in group B than in other groups（all P〈0.01）, however, the levels of TG and HDL-C were lower in group B than in other groups（all P〈0.01）. The concentrations of TC and LDL-C in group C and group D were lower than those in group A （all P〈0.01）, but the differences of the levels

关 键 词：雌激素替代疗法 内皮 血管 高脂血症 

分 类 号：R686[医药卫生—骨科学]