Dave K R, Saul I, Busto R, Ginsberg M D, Sick T J, Pérez-Pinzón M A
Cerebral Vascular Disease Research Center, Department of Neurology, University of Miami School of Medicine, Miami, Florida, USA.
J Cereb Blood Flow Metab. 2001 Dec;21(12):1401-10. doi: 10.1097/00004647-200112000-00004.
Ischemic tolerance in brain develops when sublethal ischemic insults occur before "lethal" cerebral ischemia. Two windows for the induction of tolerance by ischemic preconditioning (IPC) have been proposed: one that occurs within 1 hour after IPC, and another that occurs 1 or 2 days after IPC. The authors tested the hypotheses that IPC would reduce or prevent ischemia-induced mitochondrial dysfunction. IPC and ischemia were produced by bilateral carotid occlusions and systemic hypotension (50 mm Hg) for 2 and 10 minutes, respectively. Nonsynaptosomal mitochondria were harvested 24 hours after the 10-minute "test" ischemic insult. No significant changes were observed in the oxygen consumption rates and activities for hippocampal mitochondrial complexes I to IV between the IPC and sham groups. Twenty-four hours of reperfusion after 10 minutes of global ischemia (without IPC) promoted significant decreases in the oxygen consumption rates in presence of substrates for complexes I and II compared with the IPC and sham groups. These data suggest that IPC protects the integrity of mitochondrial oxidative phosphorylation after cerebral ischemia.
当在“致死性”脑缺血之前发生亚致死性缺血损伤时，脑内会产生缺血耐受。缺血预处理（IPC）诱导耐受存在两个窗口期：一个发生在IPC后1小时内，另一个发生在IPC后1或2天。作者检验了IPC可减轻或预防缺血诱导的线粒体功能障碍这一假设。分别通过双侧颈动脉闭塞和全身低血压（50 mmHg）2分钟和10分钟来产生IPC和缺血。在10分钟的“测试”缺血损伤后24小时收集非突触体线粒体。IPC组和假手术组之间海马线粒体复合物I至IV的氧消耗率和活性未观察到显著变化。与IPC组和假手术组相比，10分钟全脑缺血（无IPC）后24小时再灌注促进了在存在复合物I和II底物时氧消耗率的显著降低。这些数据表明IPC可保护脑缺血后线粒体氧化磷酸化的完整性。
