在总结前人与自身工作基础上，我们假设"Notch1通过NICD/Hes1等因子，作为共同环节参与RISK/SAFE/HIF-1α信号通路整合，在I-postC中发挥重要作用"，围绕"Notch1→NICD→Hes1→PTEN或DnaseⅠ→线粒体功能改变"主线，采用腺病毒载体构建等技术，制备相应转基因细胞与整体大鼠；确认已产生I-postC保护作用后，研究Notch1与Hes1不同表达水平对RISK/SAFE/HIF-1α等信号通路下游p-Akt、p-Stat3、o-PTEN及DNaseⅠ影响；探讨N1ICD、Hes1与Akt、Stat3、HIF-1α间交互作用以及在细胞内的亚定位；通过mPTP开放等功能指标，追溯上述信号通路间整合对细胞线粒体功能影响；并在整体动物比较论证。可望阐明其在I-postC心肌保护意义及相关分子机制，且可作为新的靶点，为研制新型心肌保护药物奠定的理论与实验基础。

The ischemic postconditioning (I-postC) provides protection.from myocardial injury by an unknown mechanism. Based on our preliminary absorvation.and previous report, we hypothesize that Notch1 plays an important role in I-postC.by cross talking with RISK/SAFE/HIF-1α through NICD/Hes1. By technologies including.adenovirus vector construction, we plan to establish transgenic cell and rat based.on Notch1→NICD→Hes→PTEN or Dnase I→mitochondria. After confirming the effect.of I-postC in these experimental models, we will study the effect of Notch1 and Hes1.expression level on RISK/SAFE/HIF-1α downstream molecules p-Akt, p-Stat3, o-PTEN.and DNase I. We will examine the interactions between N1ICD, Hes1, and Akt, Stat3,.HIF-1α, and the subcellular location. Based on functional parameters including mPTP.opening, we will explore the crosstalk effect of aboving cell signaling pathways.on mitochondrial function, and test it in animal model. This study will clarify the.mechanism and significance of Notch1 signaling in I-postC, and identify a novel.target to develop new myocardial protection drugs.