老龄是缺血性心力衰竭发病的高危因素，逆转心室重塑的病理生理过程是控制心衰发生的关键。我们前期研究发现ERK1/2信号通路在老龄心肌梗死后活性较年轻心肌显著下降, 但具体机制不详，CaMEK 基因转导可有效减轻老龄急性心肌缺血再灌注损伤。据此，本课题拟采用老龄小鼠缺血性心衰模型，探讨ERK1/2通路在老龄缺血性心衰中的作用及分子机制；同时，以ERK1/2信号通路为干预靶点，构建CaMEK基因的双链重组AAV-9载体，靶向转导老龄小鼠心脏，通过检测ERK1/2活性及通路中相关蛋白、线粒体功能、氧化应激、胶原表达、细胞凋亡、MMPs活性、心肌病理损害程度、心功能等指标，阐明靶向激活ERK1/2信号通路防治老龄缺血性心力衰竭的作用及分子机制，明确基因靶向干预治疗的有效性和可行性，为老龄缺血性心力衰竭的基因治疗提供新的思路和依据。

Aging is considered as a major risk factor for ischemia heart failure , to reverse the pathological and physiological cardiac remodeling process is the key factor to control the development of congestive heart failure. Recently, we have identified that the ERK1/2 signaling pathway activition in aged mice heart was significantly lower than that in youger mice suffering from myocardial infarction, but the mechanisms are not clear. Our previous studies have demonstrated that CaMEK geng transduce could activate ERK1/2 signaling pathway and result in attenuated acute myocardial ischemia-reperfusion in aged mice. So, this research will mainly explore the effects and mechanisms of ERK1/2 signal pathway in ischemic congestive heart failure of aged mice, meanwhile to select the ERK1/2 signal pathway as intervention target，to construct the double strand serotype 9 recombinant adeno-associated viral vectors containing CaMEK gene and to targetly transfect it into the heart, the research will investigate the index of ERK1/2 signal pathway activity and related proteins expression, mitochondrial function , oxidative stress, collagen protein and inflammatory factors expression, MMPs activity, myocardial pathological damage, infarct size and cardic function, et al. Meanwhile we will also investigate the targeted activation of ERK1/2 signaling pathway, prevent and cure the aging ischemic heart failure and provide the insight and molecular mechanisms of identified gene.