血管紧张素（1-7）对阿霉素扩张型心肌病大鼠心功能和心肌细胞凋亡的影响及其机制  

Angiotensin 1-7 attenuates left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopathy

作　　者：刘洪智[1] 高传玉[1] 王现青[1] 付海霞[1] 杨宏辉[1] 王宪沛[1] 刘煜昊[1] 李牧蔚[1] 牛振民[1] 戴国友[1] 齐大屯[1] 张优[1] 

机构地区：[1]河南省人民医院心内科,郑州450003

出　　处：《中华心血管病杂志》2012年第3期219-224,共6页Chinese Journal of Cardiology

基　　金：河南省科技攻关项目（1121023100240）

摘　　要：目的探讨血管紧张素（1-7）[Ang（1-7）]对阿霉素扩张型心肌病大鼠心功能及心肌细胞凋亡的影响及其机制。方法雄性Wistar大鼠分3组：（1）阿霉素扩张型心肌病组（ADR—DCM组，n=25），阿霉素2．5mg／kg，尾静脉注射，每周1次，连续10周。（2）阿霉素扩张型心肌病＋Ang（1—7）治疗组[Ang（1—7）组，n=25]，阿霉素给药方式及剂量同前，同时Ang（1-7）用Alzet2006型微量泵以24μg·kg^-1·h^-1速度持续腹腔泵入。（3）正常对照组（n=10）。12周时进行超声和血液动力学检测，硫代巴比妥酸法检测丙二醛（MDA）含量，放免法检测外周血中血管紧张素Ⅱ（AngⅡ）含量，苏木精-伊红染色法（HE染色）检测心肌病理变化，原位末端转移酶标记技术（TUNEL法）检测心肌组织细胞凋亡，免疫印迹法（Western blot）检测大鼠左心室心肌中促凋亡蛋白半胱氨酸蛋白酶3（caspase-3）、Bcl-2相关X蛋白（Bax）和抗凋亡蛋白B细胞淋巴瘤／白血病-xl（Bcl-xl）的表达。结果Ang（1-7）组病死率明显低于ADR—DCM组（16％比40％，P〈0．01）。ADR—DCM组大鼠左心室收缩末期内径（LVESD）及舒张末期内径（LVEDD）均明显大于正常对照组（P均〈0．01），左心室舒张末期压力（LVEDP）明显高于正常对照组（P〈0．01），左心室短轴缩短率（FS）及左心室压力上升（下降）最大速率（±dp／dt）明显低于正常对照组（P〈0．01）。Ang（1-7）组大鼠LVESD、LVEDD及LVEDP均明显低于ADR—DCM组（P均〈0．01），FS及±dp／dt明显高于ADR—DCM组（P〈0．01）。与正常对照组比较，Ang（1—7）组大鼠LVESD、LVEDD及LVEDP仍较高（P均〈0．01），FS及±dp／dt仍较低（P均〈0．01）。ADR—DCM组大鼠左心室心肌MDA含量及血浆AngⅡ浓度均明显高于正常对照组（P均〈0．01），而在Ang（1-7）组MDA及AngⅡ浓度显著低于ADR—DCM组（P〈0．01），但仍高�ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated eardiomyopthy （ADR-DCM）. Methods Weight-matched adult male Wistar rats were randomly divided into 3 groups ： （ 1 ） the ADR-DCM group （ n = 25 ）, in which 2. 5 mg/kg of ADR was weekly intravenously injected for 10 weeks. （2） Ang （1-7）group （n = 25 ）, in which ADR rats were simuhaneously treated with angiotensin- （1-7） （24 μg· kg^-1· h^-1 ,ip. ） for 12 weeks. （3） normal control group （n = 10）. Hemodynamics and echocardiography examination were performed at 12 weeks. The malondialdehyde （MDA） was measured by TBA methods. The plasma concentration of Ang Ⅱ was determined by immunoradiometric assay. The pathological change was analyzed by histological hematoxylin-eosin staining. Myocardial apoptosis was assessed by TUNEL method. The protein expression of pro-apoptotic protein caspase-3, Bax and antiapoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot. Results Mortality was significantly lower in Ang（1-7） group than in ADR-DCM group （ 16% vs. 40% , P 〈 0. 01 ）. Compared to the control group, left ventricular end-diastolic diameter （LVEDD） , left ventricular end systolic diameter （LVESD） and left ventricular end-diastolic pressure （LVEDP） were significantly increased in ADR-DCM group （ all P 〈 0. 01 ） while fractional shorting （ FS ）, ＋ dp/dtmax and - dp/dtmax were significantly reduced in ADR-DCM group （ all P 〈 0. 01 ）. LVEDD, LVESD and LVEDP were significantly reduced while FS, ＋ dp/dtmax and -dp/dtmax were significantly higher in Ang（1-7） group compared to the ADR-DCM group, but still higher than the control group （ all P 〈 0. 01 ）. The concentrations of Ang Ⅱ and MDA were higher in the ADR-DCM group than in the control group （ P 〈 0. 01 ） , which were significantly reduced by Ang（1-7） treatment （P 〈 0. 01 ）. The TUNEL-positive cells and apoptosis index, the expression of proapoptotic pr

关 键 词：心肌疾病 表柔比星 血管紧张素类 细胞凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]