内皮素-1受体拮抗剂对高脂血症家兔血管内皮功能的影响  

Effect of endothelin-1 receptor antagonist on the endothelial function in hyperlipidemia rabbits

作　　者：曹国良[1] 凌丹芸[1] 冯月英[1] 李晓丽[1] 

机构地区：[1]上海交通大学医学院附属第三人民医院老年科,上海524001

出　　处：《中华实用诊断与治疗杂志》2015年第6期543-545,共3页Journal of Chinese Practical Diagnosis and Therapy

基　　金：上海市宝山区科委资助项目(10-E-1)

摘　　要：目的探讨内皮素-1受体拮抗剂对高脂血症家兔血管内皮功能的影响。方法 24只雄性新西兰大白兔随机分为对照组、模型组和BQ-123干预的内皮素-1拮抗剂组(拮抗剂组),每组8只。对照组饲喂普通饲料,模型组和拮抗剂组均饲喂高脂饲料,第6周时对照组和模型组兔静脉注射生理盐水4mL/d,连续5周,拮抗剂组静脉滴注选择性内皮素A受体拮抗剂BQ-123 4mL/d,30min滴完,连续5周。10周后检测3组血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇水平;采用免疫组织化学SP法检测兔主动脉组织内皮素-1和C反应蛋白(C-reactive protein,CRP)表达水平,采用PCR法检测兔主动脉组织CRP mRNA表达情况。结果拮抗剂组血清总胆固醇[(4.12±0.92)mmol/L]、三酰甘油[(1.43±0.58)mmol/L]、低密度脂蛋白胆固醇[(1.99±0.86)mmol/L]水平均低于模型组[(6.36±1.23)、(2.14±0.70)、(2.79±0.87)mmol/L](P<0.05),血清高密度脂蛋白胆固醇水平[(2.15±0.56)mmol/L]高于模型组[(1.02±0.42)mmol/L](P<0.05);模型组和拮抗剂组动脉粥样硬化病变相对面积(32.06%、12.35%)明显高于对照组(3.78%)(P<0.01),模型组高于拮抗剂组(P<0.05);拮抗剂组内膜厚度[(226.00±4.25)μm]、中膜厚度[(142.00±1.86)μm]、内膜面积[(0.34±0.04)μm2]、中膜面积[(0.46±0.04)μm2]均较模型组[(325.00±5.68)μm、(185.00±2.07)μm、(0.52±0.04)μm2、(0.73±0.05)μm2]明显下降(P<0.05),与对照组比较差异无统计学意义(P>0.05);拮抗剂组主动脉组织内皮素-1(1.39±0.78)、CRP mRNA(3.42±1.23)水平较模型组(3.98±0.76、6.37±1.66)明显下降(P<0.05);主动脉组织中内皮素-1与CRP mRNA表达水平呈正相关(r=0.346,P=0.024)。结论内皮素-1激活的内皮素A受体可导致家兔动脉粥样硬化斑块CRP表达上调,选择性内皮素A受体拮抗剂可预防家兔动脉粥样硬化进展。Objective To observe the effect of endothelin-1（ET-1）receptor antagonist on the endothelial function in hyperlipidemia rabbits.Methods Twenty-four male New Zealand white rabbits were randomly divided into control group,model group and ET-1antagonist group,with 8rabbits in each group.Control group was fed with normal diet,while model and ET-1antagonist groups were fed with high fat diet.In 6 weeks,control and model groups were intravenously injected 4mL normal saline once a day for 5weeks,while ET-1angatonist group was intravenously injected4 mL BQ-123 within 30minutes once a day for 5weeks.The levels of total cholesterol（TC）,triacylglycerol（TG）,low density lipoprotein-cholesterol（LDL-C）and high density lipoprotein-cholesterol（HDL-C）were detected after high fat feeding for 10 weeks.The expressions of ET-1and C-reactive protein（CRP）in the aorta were detected with SP immunohistochemical staining,and CRP mRNA was detected by PCR technique.Results The levels of TC,TG and LDL-C in ET-1antagonist group（（4.12±0.92）,（1.43±0.58）,（1.99±0.86）mmol/L）were lower than those in model group（（6.36±1.23）,（2.14±0.70）,（2.79±0.87）mmol/L）（p〈0.05）,and the level of HDL-C in antagonist group（（2.15±0.56）mmol/L）was higher than that in model group（（1.02±0.42）mmol/L）（p〈0.05）.Atherosclerosis area ratio was 32.06%in model group and 12.35%in ET-1antagonist group,significantly higher than that in control group（3.78%）（p〈0.01）,and higher in model group than that in ET-1antagonist group（p〈0.05）.The endomenbrane thickness（（226.00±4.25）μm）,medimembrane thickness（（142.00±1.86）μm）,endomembrane area（（0.34±0.04）μm2）and medimembrane area（（0.46±0.04）,μm2）in antagonist group were significantly lower than those in model group（（325.00±5.68）μm,（185.00±2.07）μm,（0.52±0.04）μm2,（0.73±0.05）μm2）（p〈0.05）,showing no significant differences in comparison with those in control group（p〈0.05

关 键 词：高脂血症 内皮素-1 选择性内皮素A受体拮抗剂 家兔 动脉粥样硬化斑块 C反应蛋白 

分 类 号：R589.2[医药卫生—内分泌]