急性心肌梗死引起的再灌注损伤尚无有效治疗方法。研究指出再灌注损伤与心脏锌离子丢失为特征的锌稳态失衡有关，调节锌稳态是抗再灌注损伤的靶点之一。心脏自身分泌的心房钠尿肽（ANP）具有心肌保护作用，但与锌稳态之间的相互关系尚无报道。研究证实ANP和Zn2+均通过抑制GSK-3β活性和mPTP开放而减轻再灌注损伤；同时ANP减缓再灌注时的Zn2+丢失并增加锌转运蛋白（Zip2）的表达。PI3K/Akt/mTOR和JAK2/STAT3信号通路参与再灌注损伤的保护。但PI3K/Akt/mTOR和JAK2/STAT3、锌稳态在 ANP抵制再灌注损伤中的具体作用及其机制尚不清楚。本项目将探讨：ANP对再灌注心脏锌稳态的影响； PI3K/Akt/mTOR和JAK2/STAT3在ANP调节锌稳态及抗再灌注损伤中的作用及其机制。本项目将揭示ANP保护再灌注心脏的详细分子机制，为防止再灌注损伤提供新的靶点和思路。

There is no an effective therapeutic means for the treatment of myocardial ischemia/reperfusion injury caused by acute myocardial infarction. Zinc dyshomeostasis characterized by a loss of zinc at reperfusion has been demonstrated to contribute to cardiac reperfusion injury. Accordingly, the maintenance of zinc homeostasis is one of the important therapeutic targets for the treatment of reperfusion injury. Our recent study showed that ANP and zinc can protect the heart from reperfusion injury by preventing the mPTP opening through glycogen synthase kinase-3β. We further found that ANP can prevent zinc loss and increase the zinc transporter Zip2 expression. Studies have demonstrated that the JAK2/STAT3 and PI3K/Akt/mTOR singaling pathways have been demonstrated to play an important role in the prevention of reperfusion injury. However, it is unknown if PI3K/Akt/mTOR, JAK2/ STAT3, and zinc play a role in the cardioprotective effect of ANP at reperfusion. This project will adopt the methods of physiology, cell biology, and molecular biology to test: 1）The role of zinc in the cardioprotection with ANP. 2）The roles of the PI3K/Akt/mTOR and JAK2 / STAT3 pathways in the modulation of zinc homeostasis by ANP. This project will not only shed light on the molecular mechanism of the prevention of myocardial reperfusion injury by ANP but also provide new targets and strategies for the prevention of myocardial reperfusion injury.