Bucci M N, Black K L, Hoff J T
Section of Neurosurgery, University of Michigan, Ann Arbor.
Surg Neurol. 1990 Jan;33(1):12-4. doi: 10.1016/0090-3019(90)90217-d.
Arachidonic acid metabolites have been implicated in the development of cerebral edema following ischemia. To define the time course of metabolite production, subtemporal craniectomies were performed on 60 male Sprague-Dawley rats (350-400 g). Thirty rats underwent middle cerebral artery occlusion while 30 rats underwent craniectomy alone. Five rats in each of two groups (middle cerebral artery occlusion and sham) were sacrificed at 15 minutes, 1 hour, 4 hours, 1 day, 3 days, and 6 days. The cerebral hemispheres were removed and divided in the midsagittal plane. Each hemisphere was immediately frozen in isopentane cooled in dry ice and stored at -70 degrees C. Tissue prostaglandins E2 and 6-keto F1 alpha, and leukotrienes (LT) B4 and C4 were measured by radioimmunoassay. Prostaglandin E2 and 6-keto prostaglandin F1 alpha were significantly elevated at 15 minutes in the middle cerebral artery occlusion hemispheres (p less than 0.05). Prostaglandins were not significantly elevated after 15 minutes. LT B4 and C4 were never significantly elevated. Meclofenamate, a nonsteroidal anti-inflammatory agent, was administered to 21 additional rats. Seven controls underwent middle cerebral artery occlusion alone, 7 were given intraperitoneal meclofenamate (20 mg/kg) 30 minutes prior to middle cerebral artery occlusion, and 7 underwent middle cerebral artery occlusion followed immediately by intraperitoneal meclofenamate (20 mg/kg). The animals were sacrificed at 15 minutes and similarly studied. There was a significant reduction of prostaglandin E2 and 6-keto prostaglandin F1 alpha following pretreatment with meclofenamate (p less than 0.01 and p less than 0.05). In pretreated rats, leukotrienes were not affected by meclofenamate. Similarly, prostaglandins and leukotrienes did not change when meclofenamate was administered after middle cerebral artery occlusion. We conclude that cyclo-oxygenase metabolite production begins within 15 minutes of middle cerebral artery occlusion. Treatment with meclofenamate prior to middle cerebral artery occlusion significantly reduced cyclooxygenase metabolite production, suggesting a protective effect of meclofenamate against ischemia-induced elevations of vasoactive prostaglandins implicated in the development of cerebral edema. Lipoxygenase metabolite production was not affected by middle cerebral artery occlusion or pharmacological intervention.
花生四烯酸代谢产物与缺血后脑水肿的发生有关。为了确定代谢产物产生的时间进程，对60只雄性Sprague-Dawley大鼠（350 - 400克）进行了颞下颅骨切除术。30只大鼠接受大脑中动脉闭塞，而30只大鼠仅接受颅骨切除术。在15分钟、1小时、4小时、1天、3天和6天时，对两组（大脑中动脉闭塞组和假手术组）中的每组5只大鼠进行处死。取出大脑半球并在矢状面进行分割。每个半球立即在干冰冷却的异戊烷中冷冻，并储存在-70℃。通过放射免疫分析法测量组织中的前列腺素E2、6-酮基F1α以及白三烯（LT）B4和C4。大脑中动脉闭塞半球在15分钟时前列腺素E2和6-酮基前列腺素F1α显著升高（p < 0.05）。15分钟后前列腺素没有显著升高。LT B4和C4从未显著升高。对另外21只大鼠给予非甾体抗炎药甲氯芬那酸。7只对照大鼠仅接受大脑中动脉闭塞，7只在大脑中动脉闭塞前30分钟腹腔注射甲氯芬那酸（20毫克/千克），7只在大脑中动脉闭塞后立即腹腔注射甲氯芬那酸（20毫克/千克）。在15分钟时处死动物并进行类似研究。甲氯芬那酸预处理后前列腺素E2和6-酮基前列腺素F1α显著降低（p < 0.01和p < 0.05）。在预处理的大鼠中，白三烯不受甲氯芬那酸影响。同样，在大脑中动脉闭塞后给予甲氯芬那酸时，前列腺素和白三烯没有变化。我们得出结论，环氧化酶代谢产物的产生在大脑中动脉闭塞后15分钟内开始。在大脑中动脉闭塞前用甲氯芬那酸治疗可显著降低环氧化酶代谢产物的产生，提示甲氯芬那酸对缺血诱导的血管活性前列腺素升高具有保护作用，而血管活性前列腺素升高与脑水肿的发生有关。脂氧化酶代谢产物的产生不受大脑中动脉闭塞或药物干预的影响。
