Neuregulin-1β对阿霉素致心衰大鼠心肌细胞凋亡及bax、bcl-2蛋白表达的干预效应  

Neuregulin-1β inhibits cardiomyocyte apoptosis in adriamycin-induced rat cardiomyopathy by regulating bcl-2 and bax

作　　者：刘启亮[1] 宋耀明[1] 刘超[1] 

机构地区：[1]第三军医大学新桥医院心血管内科,全军心血管病研究所,重庆400037

出　　处：《第三军医大学学报》2009年第24期2448-2451,共4页Journal of Third Military Medical University

摘　　要：目的观察阿霉素所致心衰大鼠心肌细胞凋亡和bax、bcl-2蛋白表达情况及Neuregulin-1β(NRG-1β)的干预作用。方法60只雄性SD大鼠,体质量200～250g,分成3组:①模型组,即阿霉素心肌病组(ADR-DCM,n=20),阿霉素2mg/kg,尾静脉注射,每周1次,连续注射8周;②阿霉素心肌病+NRG-1治疗组(NRG,n=20),在注射ADR后8周后即开始给予NRG-1β10μg/(kg.d)尾静脉注射,连续5d;③正常对照组(n=20),用2ml/kg生理盐水,尾静脉注射,连续8周。9周后取心肌行HE染色病理观察,TUNEL法观察心肌细胞凋亡,Western blot检测bax、bcl-2蛋白的表达。结果模型组与NRG治疗组心肌细胞凋亡指数较正常对照组显著增高(P<0.05),与模型组相比,NRG治疗组凋亡指数显著降低(P<0.05)。与模型组比较,NRG治疗组bcl-2蛋白表达明显上调(P<0.05),bax蛋白表达明显下调(P<0.05)。结论NRG-1β能够抑制阿霉素所致心衰大鼠心肌细胞凋亡,其机制可能与bcl-2蛋白表达上调、bax蛋白表达下调、bcl-2/bax值上调有关。Objective To investigate the cardiomyocyte apoptosis and protein expressions of bcl-2 and bax in adriamycin （ADM）-induced myocardial damage in rats treated with neuregulin-1β （NRG-1β）. Methods Sixty male SD rats weighing 200 to 250 g were randomly divided into 3 groups： control, ADR-DCM and ADR ＋ NRG groups. ADR-DCM group （ n = 20） was weekly injected 2.0 mg/kg of ADR via tail vein once a week for 8 weeks to produce cardiomyopathy. The rats of ADR ＋ NRG group （ n=20） was given an injection of NRG-1β at 10 μg/（ kg·d） via tail vein for 5 d after the establishment of cardiomyopathy by ADR injection. The animals from control group （ n = 20） received 2 ml/kg normal saline by injection, once a week for 8 weeks. Nine weeks later, rats were executed under anesthesia and their heart was resected. Apoptotic cardiomyocytes were detected by using the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling （TUNEL） method. The expressions of bcl-2 and bax protein were determined by Western blotting. Results The index of apoptotic cardiomyocytes was increased significantly in ADR-DCM group and ADR ＋ NRG group compared with control group （P 〈 0. 05 ） , and compared with ADR-DCM group, the index of apoptotic cardiomyocytes was significantly lower in ADR ＋ NRG group （ P 〈 0. 05 ） ; compared with ADR-DCM group, the expressions of bcl-2 protein was increased significantly （P 〈 0.05 ）, and the expression of bax protein was induced significantly decreased in ADR ＋ NRG group （P 〈 0. 05）. Conclusion NRG-1β suppresses cardiomyocyte apoptosis induced by ADR by upregulating the expression of bcl-2 and downregulating the expression of bax.

关 键 词：neuregulin-1β 心力衰竭 心肌凋亡 BAX bcl-2 

分 类 号：R542.2[医药卫生—心血管疾病] R972.9[医药卫生—内科学]