Process of ischemic and reoxygenation injuries in organs

为了阐明缺血或缺氧损伤的过程，我们研究了缺氧时线粒体功能障碍和胞浆系统紊乱的机制，重点研究了细胞内钙的动态平衡和变化。结果表明：(1)缺氧心脏或肝脏的胞浆酶泄漏是由于缺氧时由于血流机械应力或肌肉收缩而形成的气泡破裂所致。(2)将新研制的荧光分光光度计与纤维相结合应用于灌流心脏，可实时测量细胞内钙随肌肉收缩的变化，并可直接观察缺氧和复氧过程中钙水平的变化。(3)肝脏和心脏在复氧过程中，基质酶漏出，其机制与胞浆酶漏出机制不同。(4)线粒体复氧导致基质酶漏出，同时产生过氧化氢。这不是由于磷脂酶A2的激活，而是一种钙依赖的现象，这种现象被三磷酸腺苷或环孢素A强烈抑制。这种非特异性的内膜通透性增加被认为是线粒体复氧损伤的主要原因。

In an attempt to clarify the process of ischemic or anoxic injury, we studied mechanisms involved in the dysfunction of mitochondria and disruption of cytoskelton system during anoxia, making focus on the homeostasis and variation in the intracellular level of calcium.Results obtained from the prigment study are as follows : (1) The leakage of cytosolic enzymes from anoxic heart or liver is due to disruption of blebs which have been formed during anoxia by mechanical stress of blood flow or contraction of muscles. (2) Application of a newly-developed spectrofluorophotometer combined with fiber to the perfused heart enabled to make a real-time measurement of variation of intracellular calcium in response to muscle contraction, and to directly observe changes in the calcium level during anoxia and reoxygenation. (3) In the perfused liver and heart, matrix enzymes were leaked out during reoxygenation, mechanism of which was considered to be different from that of leakage of cytosolic enzymes. (4) Reoxygenation of isolated mitochondria caused leakage of matrix'enzymes, simultaneously with the generation of hydrogen peroxide. This was not due to activation of phospholipase A2, but was a calcium-dependent phenomenon which is strongly inhibited by ATP or cyclosporin A. This non-specific increase in permeability of the inner membrane was considered to be the main cause of reoxygenation injury of mitochondria.