Herman B, Nieminen A L, Gores G J, Lemasters J J
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill 27599.
FASEB J. 1988 Feb;2(2):146-51. doi: 10.1096/fasebj.2.2.3342967.
Using low-light digitized video microscopy, the onset, progression, and reversibility of anoxic injury were assessed in single hepatocytes isolated from fasted rats. Cell-surface bleb formation occurred in three stages over 1-3 h after anoxia. Stage I was characterized by formation of numerous small blebs. In stage II, small blebs enlarged by coalescence and fusion to form a few large terminal blebs. Near the end of stage II, cells began to swell rapidly, ending with the apparent breakdown of one of the terminal blebs. Breakdown of the bleb membrane initiated stage III of injury and was coincident with a rapid increase of nonspecific permeability to organic cationic and anionic molecules. On reoxygenation, stages I and II were fully reversible, and plasma membrane blebs were resorbed completely within 6 min of reoxygenation without loss of viability. Stage III, however, was not reversible, and no morphological changes occurred on reoxygenation. The results indicate that onset of cell death owing to anoxia is a rapid event initiated by a sudden increase of nonspecific plasma membrane permeability caused by rupture of a terminal bleb. Anoxic injury is reversible until this event occurs.
利用低光数字化视频显微镜，对从禁食大鼠分离的单个肝细胞中缺氧损伤的起始、进展和可逆性进行了评估。缺氧后1 - 3小时内，细胞表面气泡形成分三个阶段。第一阶段的特征是形成大量小气泡。在第二阶段，小气泡通过合并和融合而扩大，形成一些大的终末气泡。在第二阶段接近尾声时，细胞开始迅速肿胀，最终其中一个终末气泡明显破裂。气泡膜的破裂引发了损伤的第三阶段，并且与对有机阳离子和阴离子分子的非特异性通透性迅速增加同时发生。复氧时，第一阶段和第二阶段是完全可逆的，质膜气泡在复氧后6分钟内完全被吸收，细胞活力未丧失。然而，第三阶段是不可逆的，复氧时没有发生形态学变化。结果表明，缺氧导致的细胞死亡起始是一个快速事件，由终末气泡破裂引起的非特异性质膜通透性突然增加所引发。在这一事件发生之前，缺氧损伤是可逆的。
