Target of Rapamycm, as a therapeutic target of heart failure

心力衰竭是一种与年龄相关的疾病。由于高龄是心力衰竭的主要危险因素，心脏的老化过程可能是心力衰竭的基质。尽管与年龄相关的心脏形态和功能变化已得到充分研究，但对心脏衰老的分子机制以及心脏衰老如何参与心力衰竭的发展知之甚少。最近的遗传学研究，使用短寿命的模式生物确定几个分子，发挥关键作用的生命货车决定。在已确定的分子机制中，胰岛素信号通路可能是重要的，本研究的目的是探讨胰岛素信号通路在心脏老化和热衰竭中的作用，结果如下.雷帕霉素改善扩张型心肌病动物模型的心功能.白藜芦醇可改善实验性自身免疫性心肌炎的心肌损伤.抑制胰岛素信号传导可防止小鼠心脏衰老.糖酵解的调节减轻了高血压大鼠的心力衰竭，通过调节胰岛素信号通路有望开发出治疗老年心力衰竭的新方法。

Heart failure is an age-related disease. Since advanced age is a major risk factor for heart failure, aging process of heart may he a substrate for heart failure. Although age-associated morphological and functional changes of heart are well studied, little is known about the molecular mechanism of cardiac aging and how cardiac aging is involved in the development of heart failure. Recent genetic studies using short lived model organisms identify several molecules that play critical roles in life van determination. Among the molecular mechanisms identified, insulin signaling pathway is likely to be important The purpose of this study is to examine the role of insulin signaling pathway in cardiac aging and heat failure.The results are as follows.1. Rapamycin improved cardiac function of an animal model of dilated cardiomyopathy.2. Resveratrol ameliorated myocardial injury of experimental autoimmune myocarditis.3. Suppression of insulin signaling prevented cardiac aging in mice.4. Modulation of glycolysis attenuated heart failure in a rat model of hypertension.It is hoped that a novel treatment for heart failure in older people is developed by modulating insulin signaling pathway.