目前临床匮乏缺血性心脏病保护性分子/干预靶点。申请者前期首先发现新分子CTRP3通过Akt抑制心梗后病理性心肌重构（Circulation 2012）。进一步离体预试验提示：CTRP3可显著抑制心肌缺氧/复氧损伤；CTRP3与心肌钙网蛋白（Calreticulin）直接结合；抑制Calreticulin表达可显著减低CTRP3心肌保护作用。由此提出假说：CTRP3通过受体Calreticulin发挥显著的心肌缺血/再灌注（MI/R）损伤保护作用。本研究拟采用先进的基因敲除及腺病毒过表达双向干预技术，离体细胞及动物在体研究相结合和免疫共沉淀等分子生物学的方法，通过小鼠超声、血流动力学检测、TTC染色等方法正、反向研究验证CTRP3是否通过Calreticulin发挥显著的MI/R损伤保护作用并部分阐明其机制，为缺血性心脏病防治提供新的干预靶点，具有重要的理论与应用价值。

Nowadays, clinical personnel urgently require cardioprotective molecule/intervention targets for treatment of ischemic heart disease. Applicant recently demonstrated that novel molecule CTRP3 positively regulate pathological remodeling post myocardial infarction via Akt activation (Circulation 2012). Our preliminary in vitro studies (unpublished data) suggested that: 1) CTRP3 significantly attenuated hypoxia/reoxygenation induced myocardial apoptosis; 2) CTRP3 interaction with calreticulin directly; and 3) inhibition of calreticulin expression in cardiomyocyte significantly blunt CTRP3 cardioprotection against myocardial ischemia/reperfusion injury. Thus applicant proposed scientific hypothesis that CTRP3 exerts cardioprotective actions against myocardial ischemia/reperfusion injury via calreticulin as its myocardial receptor. Utilizing calreticulin KO rats and adenovirus overexpression method, the present study will demonstrate that whether CTRP3 exerts cardioprotective actions against myocardial ischemia/reperfusion injury via calreticulin as its myocardial receptor and to identify major mechanisms involved in both in vivo and in vitro mimic myocardial ischemia/reperfusion injury models, which will provide new therapeutic target of ischemic heart disease.