老龄是急性心肌梗死(AMI)发病的高危因素。我们最近利用心肌缺血再灌注损伤（I/R）模型，发现老龄加重心肌缺血再灌注损伤的敏感性，且心肌NF-κB通路活性较对照显著激活，但机制不清楚。IκBα基因能特异性抑制NF-κB信号通路，抵抗心肌缺血损伤。据此，本课题拟采用老龄及心肌特异性IκBα转基因小鼠的I/R损伤模型，探讨NF-κB通路在老龄心肌缺血损伤易感性中的作用机制。通过构建快速表达IκBα基因的双链重组AAV9载体进行体内外转染实验，在细胞、组织及动物整体水平上，明确IκBα对NF-κB通路关键靶基因的调控，揭示NF-κB通路激活加重心肌缺血损伤的分子机制。基于老龄鼠体内外源导入IκBα干预实验，阐明靶向抑制心肌NF-κB信号通路防治老龄心肌缺血再灌注损伤的效果及分子机制，确定外源IκBα防治老龄心肌缺血损伤的效果，为减轻冠心病患者缺血再灌注损伤提供新的思路和依据。

Aging is considered as a major risk factor for acute myocardial infraction. Recently, we found that aging increased the sensitivity of myocardial ischemia-reperfusion injury in a myocardial ischemia-reperfusion injury(I/R)mouse model. Compared with the control group, the cardiac NF-κB pathway activity significantly increased, but the mechanism is not clear. IκBα gene can specifically inhibit NF-κB signaling pathway to protect against myocardial ischemic injury. Accordingly, to explore the susceptible mechanism of NF-κB pathway in aging related myocardial ischemia, this study intends to use the myocardial ischemia-reperfusion injury model in aged wild-type and transgenic mice that can express the mutant IκBα in a cardiac-specific manner. By constructing the double-stranded recombinant AAV9 vector which can express IκBα gene rapidly in vivo and in vitro transfection experiments , the role of IκBα in regulating critical target genes of NF-κB pathway at the cellular, tissue and animal level could be clarified, and then the molecular mechanism that NF-κB pathway overactivation promotes myocardial ischemic injury could be revealed. Based on the intervention experiments of exogenous IκBα importation in aged mice, the effect and molecular mechanism of targeted inhibition of NF-κB signaling pathway could be identified in the prevention of myocardial ischemia-reperfusion injury from aging. The utility of exogenous IκBα as a novel therapeutic target for aged myocardial ischemic injury would be confirmed. The study would also provides new ideas and basis to alleviate and improve the prognosis of ischemia-reperfusion injury in patients with coronary heart disease.