Cardiac ischemia reperfusion injury

当供应心脏的动脉（冠状动脉）突然关闭，剥夺心肌的血液营养和氧气（缺血）时，心脏病发作（心肌梗死）就发生了。冠状动脉长时间关闭会对心肌造成不可逆转的损伤。最先进的治疗方法是用导管重新打开阻塞的动脉，这可能导致额外的心脏损伤（再灌注损伤）。最近，Zapol博士（我建议的导师）实验室的研究人员已经证明，吸入低浓度的一氧化氮（NO）气体可以减少小鼠的再灌注损伤。NO可以通过激活可溶性鸟苷酸环化酶（sGC）来发挥作用，sGC是一种产生细胞内第二信使cGMP的酶。拟议研究计划的目标是了解NO如何保护心脏，特别是sGC和cGMP的作用。为了实现这一目标，将在项目合作者Brouckaert博士（根特大学）的实验室中研究缺乏关键sGC亚基α1的小鼠。预计这些研究将有助于了解吸入一氧化氮在动物模型中保护心脏免受缺血再灌注损伤的细胞和生化机制。因此，我们获得的结果很可能为创新治疗概念的策略发展提供必要的知识。

A heart attack (myocardial infarction) occurs when an artery supplying the heart (coronary artery) suddenly closes depriving heart muscle of blood nutrients and oxygen (ischemia). Prolonged closure of a coronary artery can irreversibly damage heart muscle. The state of the art treatment is the reopening the blocked artery with catheters, which can lead to additional heart damage (reperfusion injury). Recently, investigators in the laboratory of Dr. Zapol (my proposed mentor) have shown that low concentrations of inhaled nitric oxide (NO) gas can reduce reperfusion injury in mice. NO can exert its effects by activating soluble guanylate cyclase (sGC), an enzyme which produces the intracellular second messenger cGMP. The goal of the proposed research program is to understand how NO protects the heart and, in particular, the role of sGC and cGMP. To accomplish this goal, mice deficient in a critical sGC subunit α1 will be studied, generated in the laboratory of the project collaborator Dr. Brouckaert (University of Ghent). It is anticipated that these investigations will help to understand the cellular and biochemical mechanisms by which inhaled NO can protect the heart against ischemia and reperfusion injury in animal models. Therefore, it is very likely that our gained results will provide essential knowledge for the development of strategies to innovative therapeutic concepts.