奥美沙坦对肾性高血压大鼠心肌ACE2/Ang(1-7)/Mas的影响  

Influence of Olmesartan to renovascular hypertension rats on ACE2/Angiotensin(1-7)/Mas Receptor

作　　者：郑宏健[1] 卢新政[1] 黄红娟[1] 宗文纳[1] 杨晓慧[1] 陈秀梅[1] 雍永宏[1] 曹克将[1] 黄峻[1] 

机构地区：[1]南京医科大学第一附属医院心内科,210029

出　　处：《中华临床医师杂志（电子版）》2012年第10期94-99,共6页Chinese Journal of Clinicians(Electronic Edition)

摘　　要：目的研究奥美沙坦对肾血管性高血压大鼠心肌肥厚的作用,探讨其对病理性肥厚心肌ACE2/Ang(1-7)/Mas的作用。方法清洁级雄性SD大鼠68只,随机分为假手术组(S)18只、两肾一夹组(two kidney one clip,2K1C)50只。S组分离左肾动脉而不缩窄;实验组采用2K1C方法制备高血压模型。术后第4周末采用尾动脉袖法测量大鼠血压,造模成功大鼠(44只)随机分为2K1C+蒸馏水组(K)22只与2K1C+奥美沙坦组(O)22只。术后第5周始O组以奥美沙坦3mg.kg-1.d-1灌胃;K组每天以等体积蒸馏水灌胃。术后第8、12、14周,测量大鼠血压,超声心动图观察心脏结构及功能,酶联免疫吸附技术(ELISA)检测动脉血浆Ang(1-7)水平。实时荧光定量PCR检测心肌血管紧张素转换酶2(ACE2)及Ang(1-7)受体Mas mRNA表达,免疫印迹技术检测P-ERK1/2、Mas及ACE2蛋白水平。结果 (1)术后4、8、12、14周K组收缩压明显升高,药物灌胃后明显降低(P均<0.01);(2)术后第8、12、14周,K组大鼠舒张末期及收缩末期室间隔厚度、舒张末期及收缩末期左心室后壁厚度、左心室质量指数均明显增加,药物灌胃后明显改善(P均<0.01);(3)K组血清Ang(1-7)水平在8、12周时明显升高(P均<0.01),14周时恢复正常(P>0.05),与K组比,O组Ang(1-7)水平8周时降低,在12、14周时明显升高(P均<0.01);(4)K组ACE2及Mas基因及蛋白水平8周时均上调,12、14周时均下调,p-ERK1/2各时间段表达均升高(P均<0.01);与K组比较,O组两基因及蛋白水平8周时明显降低,在12、14周时明显升高,P-ERK1/2各时间段表达均降低(P均<0.01)。结论 2K1C法成功制作肾性高血压大鼠模型并导致明显左心室肥厚;奥美沙坦明显降低肾性高血压大鼠血压、改善左心室肥厚,抑制血清Ang(1-7)水平及组织Mas、ACE2基因与蛋白水平下调。其改善心肌肥厚作用与其作用于Ang(1-7)/Mas/ERK1/2信号通路有关。Objective To study the changes of ACE2/Angiotensin（ 1-7）/Mas Receptor axis in renovascular hypertension rats and explore the cardioprotective mechanism of Olmesartan on myocardial hypertrophy. Methods 68 Male Sprague-Dawly rats weighting 180-200 g were randomly divided into sham operation group （S, n = 18 ）, 2 kidney 1 clip （ 2K1C ） group （ K, n = 50 ）. 2K1C hypertension model was established in Sprague-Dawly rats by chronic partial occlusion of left renal artery. S group rats were performed the open-abdomen surgery without being restricted any renal artery. At the end of the fourth week, the blood pressure were taken by tail artery sleeve method, and then the K group rats （n = 44 ）those hypertension model were successfully established were randomly divided into 2K1C ＋ distilled water group （ K, n = 22 ） ,2K1C ＋ Olmesartan group （ O, n = 22 ）. Beginning from the fifth week after the surgery,the K group rats were given intragastic infusion of distilled water 10 ml kg-l d-1 ,the O group rats received Olmesartan 3 mg kg-1 d-1. Rats were measured the systolic blood pressure （SBP）at the 8th, 12th and 14th week respectively. Furthermore, the uhrasonography were taken for every group rats at the 8th, 12th and 14th week. After that, the weight of the body and left ventricle were collected by electronic balance, the plasma Ang（1-7） was evaluated by ELISA, the mRNA levels of ACE2, Mas were detected by RT-PCR, the protein expressions of ACE2,Mas and p-ERK1/2 were tested by western blot. Results （ 1 ） The blood pressure of K group increased significantly compared with S group （ P 〈 0.01 ） at the end of the 4th, 8th, 12th and 14th week respectively. After being treated with Olmesartan, it decreased markedly （P 〈 0. 01, respectively）. （2）The end-diastolic ventricular septal thickness, end-systolic ventricular septal thickness, end-diastolic left ventricular wall thickness, end-systolic left ventricular wall thickness and left ventricular mass index in K group we

关 键 词：高血压 血管紧张素转换酶2 血管紧张素-(1-7) MAS 奥美沙坦 心肌肥厚 

分 类 号：R544.1[医药卫生—心血管疾病]