2010-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/642614摘要：目前對於大腦缺血再灌流傷害的有效治療仍然有限。吾人假設一種新的後制約再灌流方法可以減少再灌流傷害所引起的神經細胞傷害。我們的目標在於探討這種缺血後制約訓練的有效性和其機制。特定的計畫目標包括(1) 第一年:建立大腦短暫缺血傷害的缺血後制約訓練的活體大鼠模式，以及建立體外腦皮質神經細胞培養的缺氧後制約訓練模式，並以微陣列技術探討後制約訓練誘發的基因表現。(2) 第二年: 使用藥物抑制劑來探討粒線體滲透度移轉(MPT)和需能鉀離子(mitoKATP)通道在缺血後制約訓練所扮演的功能性角色。(3) 第三年: 使用藥物抑制劑方法來研究再灌流傷害救援激素RISK途徑在後制約訓練的依時表現方式和功能性角色，以及探討後制約訓練對凋亡途徑PIDD 訊息的抑制效果。吾人初步結果顯示缺血後制約訓練和缺氧後制約訓練均可有效減少缺血再灌流所導致的神經細胞死亡，後制約訓練的保護效果和調節粒線體功能異常以及再灌流傷害救援激素的表現有關。吾人預期缺血後制約訓練對於減少神經細胞再灌流傷害的研究將有助於發展再灌流傷害的基礎研究以及相關的標靶治療。<br> Abstract: Effective strategies to reduce reperfusion injury after cerebral ischemia are limited.We test our hypothesis that a new postconditioning maneuver would mitigatereperfusion injury of neuronal ischemia. Our goals are to explore the effectiveness andmechanisms of ischemic postconditioning on cerebral ischemia. The specific aimsinclude (1) 1st year: the establishment of an in vivo model of ischemicpostconditioning on transient cerebral ischemia and an in vitro model of hypoxicpostconditioning on cortical neuron cultures, then explore the early gene responseunderlying ischemic postconditioning microarray; (2) 2nd year: the characterization ofthe roles of mitochondrial permeability transit and mitochondrial ATP-dependentpotassium channel in the protective mechanism of ischemic postconditioning by usingpharmacological inhibitors; (3) 3rd year: the characterization of the roles and temporalexpression of reperfusion injury salvage kinases pathway in the protective mechanismof ischemic and hypoxic postconditioning by using pharmacological inhibitors, andthe impact of ischemic postconditioning on proaptotic PIDD signaling. Ourpreliminary data shows that ischemic and hypoxic postconditioning could effectivelyreduce neuronal death after ischemia-reperfusion injury. The protection ofpostconditioning is associated with the modulation of mitochondrial dysfunction andexpression of reperfusion injury salvage kinases. We expect that the study of ischemicpostconditioning on cerebral ischemia would contribute to the development oftargeted therapies against reperfusion injuries.