压力超负荷所致心肌肥厚中程序性坏死的初步研究  

Preliminary Study of Necroptosis in Cardiac Hypertrophy Induced by Pressure Overload

作　　者：赵明月[1] 秦育培 陆立慧 汤小菊[1] 吴文超[1] 付华[2] 刘小菁[1] 

机构地区：[1]四川大学华西医院再生医学研究中心心血管疾病研究室,成都610041 [2]四川大学华西医院心内科,成都610041

出　　处：《生物医学工程学杂志》2015年第3期618-623,共6页Journal of Biomedical Engineering

基　　金：国家自然科学基金资助项目(11072163,11372204);高等学校博士学科点基金资助项目(20120181110012);四川省科技厅资助项目(2010FZ0092)

摘　　要：本研究旨在观察压力超负荷所致心肌肥厚的病理生理过程中是否发生细胞程序性坏死及洛沙坦对这一病理生理过程的影响。实验采用腹主动脉缩窄术(TAC)建立压力超负荷导致的心肌肥厚大鼠模型,通过动脉血压、超声心动图、左心室质量指数、心肌肥厚分子标志物等观察左心室的结构功能变化。用real-time PCR和Western blot法分别检测程序性坏死标志物——受体相互作用蛋白激酶1和3(RIPK1和RIPK3)的基因和蛋白表达变化。结果表明,SD大鼠TAC术后4周可发生心肌肥厚。心肌组织中RIPK1/RIPK3的表达升高,HE染色发现坏死样心肌组织,电镜结果显示线粒体结构受损,提示心肌细胞可能发生程序性坏死。给予TAC大鼠血管紧张素Ⅱ受体拮抗剂洛沙坦治疗,大鼠心脏结构及功能明显改善,心肌肥厚程度减轻,而且对心肌肥厚过程中的程序性坏死有明显的抑制作用。The aim of this study was to observe whether necroptosis is involved in the process of cardiac hypertrophy induced by pressure overload.SD rats underwent transverse abdominal aortic constriction（TAC）operation for establishing cardiac hypertrophy model.The structure and function of the left ventricle of rats were evaluated via echocardiography,left ventricular mass index,the expression of markers of cardiac hypertrophy and histological detection.Real-time PCR and Western blot were used to measure the gene and protein expression of receptor interacting protein kinase 1and 3（RIPK1and RIPK3,the necroptosis markers）respectively.Four weeks after TAC operation,rat model for cardiac hypertrophy was established.The experimental data showed that the gene and protein expressions of RIPK1 and RIPK3in the rat heart hypertrophic tissues after TAC for 4weeks were increased significantly compared with those in the sham group.HE staining showed cardiomyocytes injury and hypertrophy in the hearts of TAC rat models.By transmission electron microscope,we observed that mitochondria of cardiomyocytes were damaged seriously in the TAC models.Treatment with losartan used,the selective antagonist of angiotensin ⅡtypeⅠreceptor could improve the cardiac function of TAC rats.Moreover,losartan treatment decreased the expression of RIPK1 and RIPK3in heart tissues of TAC rats.The results suggest that necroptosis occurrs in the process of cardiac hypertrophy with pressure overload,and losartan could alleviate the cardiac hypertrophy and inhibit necroptosis.

关 键 词：程序性坏死 洛沙坦 压力超负荷 腹主动脉缩窄 

分 类 号：R542.2[医药卫生—心血管疾病]