Watkins M T, Haudenschild C C, al-Badawi H, Velazquez F R, Larson D M
Department of Surgery, Boston University School of Medicine, University Hospital, Boston University Medical Center, Massachusetts 02118.
Am J Physiol. 1995 Feb;268(2 Pt 2):H749-58. doi: 10.1152/ajpheart.1995.268.2.H749.
We have studied endothelial functions and integrity under clinically relevant levels of acute and profound hypoxia. Bovine aortic endothelial cells (EC) grown on microcarrier beads were exposed for 15-min intervals to normoxic (20% O2) or hypoxic (1-2% O2) medium. Control intervals were followed by four hypoxic and then four normoxic intervals for reoxygenation. Prostacyclin release from EC significantly decreased after only 15 min of hypoxia and remained low despite reoxygenation. This decrease in prostacyclin release was not coincident with decreased viable cells (Trypan blue exclusion) or with increased cell lysis (increased lactate dehydrogenase) after hypoxia or reoxygenation. When the medium was supplemented with 30 microM arachidonate (saturating concentration), prostacyclin release still significantly decreased after 30 min of hypoxia but returned to baseline levels by 30 min of reoxygenation. Similar results were obtained for thromboxane B2 release. These data suggest that 1) EC decrease prostacyclin release during acute, profound hypoxia, 2) EC decrease prostaglandin production during hypoxia despite abundant exogenous arachidonate, and 3) recovery of prostaglandin production is dependent on exogenous arachidonate during reoxygenation.
我们研究了在临床相关水平的急性严重缺氧情况下内皮细胞的功能和完整性。将生长在微载体珠上的牛主动脉内皮细胞（EC）每隔15分钟暴露于常氧（20% O₂）或低氧（1 - 2% O₂）培养基中。对照组先进行四个低氧时间段，然后进行四个常氧时间段以进行复氧。仅缺氧15分钟后，EC释放的前列环素就显著减少，且尽管进行了复氧，仍维持在低水平。这种前列环素释放的减少与缺氧或复氧后活细胞数量减少（台盼蓝排斥法）或细胞裂解增加（乳酸脱氢酶增加）并不一致。当培养基中添加30微摩尔花生四烯酸（饱和浓度）时，缺氧30分钟后前列环素释放仍显著减少，但复氧30分钟后恢复到基线水平。血栓素B₂释放也得到了类似结果。这些数据表明：1）在急性严重缺氧期间，EC减少前列环素释放；2）尽管有大量外源性花生四烯酸，EC在缺氧期间仍减少前列腺素生成；3）复氧期间前列腺素生成的恢复依赖于外源性花生四烯酸。
