厄贝沙坦对大鼠心肌细胞凋亡及Bcl-2/Bax蛋白表达的影响  

Effect of irbesartan on the cardiomyocyte apoptosis and expression of Bcl-2/Bax proteins in rats

作　　者：邓利芝[1] 万新红 冯欣蘅[1] 李炯[1] 林小荣[1] 陈金龙[1] 黄建明[3] 

机构地区：[1]汕头大学医学院第二附属医院急诊科,广东省汕头市515041 [2]深圳龙岗区人民医院内科,广东省汕头市518172 [3]汕头大学医学院病理生理研究室,广东省汕头市515031

出　　处：《中国临床康复》2004年第24期4998-5000,共3页Chinese Journal of Clinical Rehabilitation

基　　金：广东省医学科研基金(B1998103;B1998104)~~

摘　　要：目的观察自发性高血压大鼠(spontaneouslyhypertensiverats,SHR)心肌细胞凋亡和Bax/Bcl-2蛋白的表达;同时观察血管紧张素Ⅱ-1型受体(angiotensinⅡ1typereceptor,AT1R)拮抗剂-厄贝沙坦对SHR大鼠心肌细胞凋亡和BcL-2/Bax蛋白表达的影响。方法24只16周龄SHR大鼠(上海市高血压研究所提供,医动字02-37-1号)分为SHR治疗组[沙坦30mg/(kg·d),20周]和SHR对照组,另选16周龄Wistar大鼠12只作为正常对照组。分别采用SP免疫组化法和末端脱氧核苷酸转移酶介导dUTP缺口末端标记法方法检测心肌细胞凋亡指数和BcL-2/Bax蛋白水平的表达,放射免疫法检测血浆和组织血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)。结果SHR治疗组与正常对照组比较收缩压明显增高[(243±13)和(151±11)mmHg,1mmHg=0.133kPa],左心室质量与体质量比(leftventricularmass/bodymass,LVW/BW)明显增加[(4.05±0.33)和(2.90±0.23)g/kg];血浆和心肌组织AngⅡ增高[血浆(31.8±5.4)和(22.2±18.5)ng;心肌(13.2±2.1)%和(8.3±1.2)%];心肌细胞凋亡指数明显增加[(4.75±0.70)%和(2.84±0.60)%];心肌细胞Bax蛋白的表达明显增强[(5.02±0.34)%和(2.85±0.29)%],Bcl-2/Bax比率明显降低(0.65±0.13和1.05±0.18),差异有显著性意义(P<0.05～0.01);而Bcl-2蛋白的表达[(3.AIM:To investigate the cardiomyocyte apoptosis and the expression of proteins Bcl 2/Bax and the effects of angiotensinⅡ 1 type receptor(AT1R) antagonist irbesartan on the cardiomyocyte apoptosis and the expression of proteins Bcl 2/Bax in the left ventricle of spontaneously hypertensive rats(SHR).METHODS:Twenty four SHR,aged 16 weeks old (provided by the Shanghai Research Institute of Hypertension, No. 02 37 1), were randomized into two groups: SHR treatment group (n=12) and SHR control group (n=12), another 16 Wistar rats were selected as the normal control group. Rats in the SHR treatment group were treated with irbesartan 30 mg/kg per day for 20 weeks. The apoptosis index of cardiomyocyte and the expressions of proteins Bcl 2 and Bax were detected by using SP immunohistochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), and the angiotensin Ⅱ(AngⅡ) in plasma and tissues were determined with the radioimmunoassay. RESULTS: Compared with the normal control group, the systolic pressure [(151±11) vs(243±13) mm Hg,1 mm Hg=0.133 kPa), left ventricular mass/body mass (LVM/BM) [(2.90±0.23) vs (4.05±0.33) g/kg]were obviously increased,AngⅡin plasma [(22.2±18.5) vs (31.8±5.4) ng] and tissues [(8.3±1.2) vs (13.2±2.1) ng]were increased,apoptosis index of cardiomyocyte [(2.84±0.60)%vs (4.75±0.70)%) was increased obviously,expression of Bax protein [(5.02±0.34)%vs (2.85±0.29)%] and the ratio of Bax was obviously decreased [(0.65±0.13) vs (1.05±0.18)] in the SHR treatment group,and there were significant differences(P< 0.05-0.01),while there was no significant difference in the expression of Bcl 2 protein [(3.29±0.24)%vs (2.95±0.29)%] between the SHR treatment group and normal control group.The systolic pressure,LVMI,apoptosis index of cardiomyocyte,and expression of Bax protein were obviously reduced,while Bcl 2/Bax,AngⅡin plasma and tissues in the SHR treatment were increased as compared with those in the SHR control group,which were(179±11) mm Hg,(3.22±0.

关 键 词：厄贝沙坦 大鼠 心肌细胞凋亡 Bcl-2 BAX 自发性高血压 血管紧张素Ⅱ-1型受体拮抗剂 

分 类 号：R544.1[医药卫生—心血管疾病] R972.4[医药卫生—内科学]