佐芬普利对肾血管性高血压大鼠肥厚心肌血管紧张素转换酶2/血管紧张素(1-7)/Mas与转化生长因子β_1水平的影响  

Effects of zofenopril on expressions of angiotensin-converting enzyme2/angiotensin (1-7)/Mas and transforming growth factor-beta 1 in hypertrophied myocardium of renovascular hypertensive rats

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,江苏南京210029

出　　处：《中华高血压杂志》2013年第1期41-47,共7页Chinese Journal of Hypertension

摘　　要：目的研究肾血管性高血压大鼠肥厚心肌中血管紧张素转换酶2(ACE2)/血管紧张素(1-7)[Ang(1-7)]/Mas轴及转化生长因子β1(TGF-β1)的变化,探讨佐芬普利改善其心肌肥厚的机制。方法清洁级雄性SD大鼠68只,分为假手术组(n=18)和模型组(n=50)。模型组用两肾一夹法制备高血压模型。术后4周末,将成功造模大鼠随机分为模型组(n=22)和佐芬普利组(n=22)。佐芬普利组以佐芬普利10mg/(kg·d)灌胃;术后8、12、14周末,测量血压,行心脏超声观察心脏结构及功能,酶联免疫吸附试验(ELISA)检测动脉血清Ang(1-7)及TGF-β1水平,RT-PCR检测心肌细胞ACE2、Mas及TGF-β1 mRNA水平,Western blot检测ACE2及Mas蛋白水平。结果①模型组大鼠收缩压升高,室间隔厚度、左心室后壁厚度增加,佐芬普利组血压降低,心室肥厚改善(均P<0.01)。②与假手术组比,模型组大鼠动脉血清Ang(1-7)水平在8、12周时较高;与模型组相比,佐芬普利组Ang(1-7)水平8周时较低,12、14周时较高。③术后8、12、14周,模型组动脉血清TGF-β1水平均高于假手术组和佐芬普利组[8周:(22.03±1.09)比(14.22±1.24)比(16.29±1.41);12周:(23.95±1.41)比(14.26±1.28)比(14.39±1.38);14周:(25.91±1.59)比(13.98±1.07)比(14.48±1.52)ng/L;均P<0.01]。④与假手术组和佐芬普利组比较,模型组大鼠心肌Mas、ACE2mRNA及蛋白水平8周时较高,12、14周时较低(均P<0.01)。结论佐芬普利明显降低肾血管性高血压大鼠的血压,改善左心室肥厚,并与其抑制血清Ang(1-7)水平及组织Mas、ACE2基因与蛋白水平下调,抑制血清及心肌TGF-β1水平上调有关。Objective To study the changes of angiotensin-converting enzyme 2 （ACE2）/angiotensin （1-7） [Ang（ 1-7）]/Mas axis and transforming growth factor-beta I（TGF-β1 ） in renovascular hypertensive rats and explore the cardioprotective mechanism of zofenopril on myocardial hypertrophy. Methods A total of 68 male Sprague- Dawly rats were randomly divided into sham-operation group （ n = 18） and 2-kidney, 1-clip （2KIC） group （n= 50）. 2K1C hypertensive model was established. The systolic hood pressure （SBP） was measured by the tail-cuff method 4 weeks later. The hypertensive rats were randomly divided into model group （n =22） and zofenopril [10 mg/ （kg·d）] group （n=22}. Postoperative SBP measurements were performed 8, 12 and 14 weeks later, respectively. Cardiac structure and function were assessed by cardiac ultrasonography. SBP, cardiac ultrasonography were measured at the 8th, 12th and 14th week respectively. The plasma Ang（1-7） and TGF-β1 were evaluated by ELISA, the mRNA levels of ACE2, Mas and TGF-β1 detected by RT-PCR, and the protein levels of ACE2 and Mas receptor tested by Western blotting. Results ①The SBP,ventricular septal thickness and posterior left ventricular wall thickness increased significantly in 2K1C rats, while lower SBP and reversed ventricular hypertrophy was notedin zofenopril group （ both P〈0.01）. ②The plasma Ang（1-7） was higher in hypertensive model group than in sham operation group at the 8th and 12th week. After being given zofenopril, Ang（1-7） increased sharply at the 12th and 14th week except the 8th week. ③The serum levels of TGF-β1 were significantly higher in model group than in sham-operation group and zofenopril group at each time point[ 8th week： （ 22.03± 1.09 ） vs （ 14.22 ± 1.24） vs （16.29±1.41）; 12thweek： （23.95±1.41） vs （14.26±1.28） vs （14.39±1.38）; 14thweek： （25.91±1.59） vs （13.98±1.07） vs （14.48±1.52）ng/L; all P〈0. 011. ④In contrast to those of sham-operation

关 键 词：佐芬普利 高血压 心肌肥厚 血管紧张素转换酶2 转化生长因子β1 

分 类 号：R544.1[医药卫生—心血管疾病]