L-BM诱导的血流动力学改变对慢性心衰中自噬的调控和机制研究

项目名称： L-BM诱导的血流动力学改变对慢性心衰中自噬的调控和机制研究

项目编号： No.31300774

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 关溯

作者单位： 华南理工大学

项目金额： 23万元

中文摘要： 慢性心衰（Chronic heart failure, CHF）是临床上常见的心血管系统疾病。各种心血管疾病引起血流动力学紊乱，心肌负荷过重，代偿性肥厚，进而发展为心肌细胞死亡是CHF主要的病理生理机制。自噬是心肌细胞在血流动力学应激下一种重要的死亡方式。左旋盐酸班布特罗（L-Bambuterol, L-BM）属长效beta2肾上腺素受体（β2 adrenergic receptor， β2AR）激动剂。较多研究显示，β2AR激动剂能够改善血流动力学紊乱，减少心肌细胞死亡，减缓CHF的发展进程，但具体机制并不明确。另有研究显示，自噬与血流动力学改变引起的CHF密切相关。本项目拟用细胞生物学、分子生物学、离体心脏灌流等方法，研究L-BM诱导的血流动力学改变对CHF模型大鼠和心肌细胞自噬的调控和机制，阐明L-BM在CHF中的药理作用，为深入认识CHF的病理生理过程，临床药物开发提供理论依据。

中文关键词： 压力超负荷型心衰；血流动力学；β2受体激动剂；凋亡；

英文摘要： Chronic heart failure (CHF) is a common clinical cardiovascular system diseases, is the main cause of death. Hemodynamic disturbances caused by a variety of cardiovascular diseases, leading to myocardial overload, compensatory cardiomyocytes hypertrophy, then cardiomyocytes death is a major pathophysiological mechanisms of chronic heart failure. There are many ways of cardiomyocytes' death under hemodynamic stress, autophagy is an important way. L-Bambuterol (L-BM) is a long-acting beta2-adrenergic receptor (β2AR) agonists. It's major application is to treat respiratory diseases, such as asthma. Due to β2AR is also expressed in heart; bambuterol used in heart disease drew a lot of attention in recent years. Many studies have shown, β2AR agonists can improve hemodynamic disturbances, slow down the process of heart failure development and prolong survival of rats with heart failure, but the exact mechanism is not clear. Some studies showed that autophagy is closely related to the development of hemodynamic stress induced heart failure. The current project intends to use methods such as cell biology, molecular biology, and isolated rats' heart perfusion, study the effects of L-bambuterol induced hemodynamic change on autophagy in chronic heart failure rat model and cardiomyocytes, and the mechanisms, illustrate the

英文关键词： Pressure overload heart failure；Hemodynamics；Beta-2 adrenergic receptor agonist；Apoptosis；