替米沙坦对高血压大鼠血管ACE2表达及氧化应激水平的影响  

Effects of Telmisartan on vascular ACE2 expression and oxidative stress levels in spontaneously hypertensive rats

作　　者：金海燕[1] 钟久昌[1,2] 宋蓓[1,2] 叶佳颖[3] 张丽红[4] 李宇琳[1,2] 于茜[3] 徐旭东[1] 林国珍[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院临床心理科与医学基因组学国家重点实验室,上海200025 [2]上海市高血压研究所,上海市血管生物学重点实验室,上海200025 [3]宁波大学医学院分子高血压研究室,浙江宁波315211 [4]复旦大学上海医学院解剖与组织胚胎学系,上海200032

出　　处：《中国药理学通报》2012年第1期54-58,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30973522,81170246);上海市浦江人才计划项目(No 11PJ1408300);上海交通大学医学院“新百人计划”项目

摘　　要：目的探讨替米沙坦干预对自发性高血压大鼠(SHR)血管组织血管紧张素转换酶2(ACE2)基因表达、一氧化氮(NO)及氧化应激水平的影响。方法选取10周龄SHR及其同源对照WKY大鼠,分别给予替米沙坦(5、10 mg.kg-1.d-1)或安慰剂,为期10周。采用Western blot检测治疗后大鼠主动脉组织中ACE2蛋白及内皮型NO合酶(eNOS)磷酸化水平。分别采用硝酸还原酶比色法与硫代巴比妥酸比色法测定大鼠主动脉组织中NO和丙二醛(MDA)含量。结果与WKY对照组相比,SHR大鼠主动脉组织中ACE2蛋白和Ser1177-eNOS磷酸化水平明显降低(ACE2:0.39±0.05vs 1.00±0.06;p-eNOS:0.43±0.06 vs 1.00±0.04;P值均<0.01),伴NO水平下调及MDA含量增加(NO mmol.g-1protein:11.5±2.1 vs 27.8±4.9;MDA nmol.g-1 protein:393.9±17.9 vs 186.3±14.5;P值均<0.01),而经替米沙坦治疗后SHR低、高剂量治疗组大鼠主动脉组织中ACE2蛋白和Ser1177-eNOS磷酸化水平增加(ACE2:0.62±0.06,0.65±0.07 vs 0.39±0.05;p-eNOS:0.68±0.07,0.71±0.06 vs0.43±0.06;P值均<0.05),伴NO水平升高(19.2±3.3,23.9±3.2 vs 11.5±2.1 mmol.g-1protein;P值均<0.05)与MDA含量下调(271.9±16.1,249.2±19.6 vs 393.9±17.9nmol.g-1protein;P值均<0.05)。结论长期替米沙坦治疗通过提升高血压大鼠血管ACE2表达及eNOS磷酸化水平,可促使血管NO生成及氧化应激水平改善,提示替米沙坦对高血压具有一定的血管保护功效。Aim To investigate the influences of Telmisartan on vascular expression of angiotensin-converting enzyme 2（ACE2）,nitric oxide（NO） and oxidative stress levels in spontaneous hypertension rats（SHR）.Methods 10-week SHR and Wistar-Kyoto（WKY） rats were treated with Telmisartan（5 or 10 mg·kg-1·d-1） or placebo for 10 weeks.The protein and phosphorylation levels of ACE2 and endothelial NO synthase（eNOS） in the aortas from treated rats were determined with Western blotting methods.In addition,concentration of malonyldialdehyde（MDA） and NO in the rat aortas were determined with thiobarbituric acid（TBA） reactive substances and the Greiss reagent,respectively.Results Compared with WKY rat,ACE2 protein and the phosphorylated Ser1177-eNOS level were significantly reduced in the SHR aortas（ACE2：0.39±0.05 vs 1.00±0.06;p-eNOS： 0.43±0.06 vs 1.00±0.04;P0.01,respectively）,accompanied by reduced NO level and elevated MDA content（NO mmol·g-1 protein： 11.5±2.1 vs 27.8±4.9;MDA nmol·g-1 protein： 393.9±17.9 vs 186.3±14.5;P0.01,respectively）.Treatment with low-and high-dose Telmisartan significantly enhanced ACE2 protein and the phosphorylated Ser1177-eNOS level in the SHR aortas（ACE2：0.62±0.06,0.65±0.07 vs 0.39±0.05;p-eNOS： 0.68±0.07,0.71± 0.06 vs 0.43±0.06;P0.05,respectively）,along with a marked increase in NO level（19.2±3.3,23.9±3.2 vs 11.5±2.1 mmol·g-1 protein;P0.05,respectively） and an obvious reduction of MDA content（271.9±16.1,249.2±19.6 vs 393.9±17.9 nmol·g-1 protein;P0.05,respectively）.Conclusion Chronic Telmisartan treatment improves vascular expression of ACE2 and phosphorylation activation of eNOS,contributing to the augmentation of NO generation and attenuation of oxidative stress levels in SHR,suggesting that Telmisartan has potential vascular protective effects in hypertension.

关 键 词：替米沙坦 高血压 血管紧张素转换酶2 一氧化氮 氧化应激 血管保护 

分 类 号：R-332[医药卫生] R322.12