Lee S H, Kondoh T, Camarata P J, Heros R C
Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Neurosurgery. 1996 Mar;38(3):517-21; discussion 522. doi: 10.1097/00006123-199603000-00020.
A novel 21-aminosteroid (U-74389G), a new potent antioxidant, was evaluated for its protective effect on transient global cerebral ischemia. Ischemia was induced by 20 minutes of four-vessel occlusion in adult male Wistar rats. Injection of 21-aminosteroid (U-74389G, 5 mg/kg intraperitoneally injected) was repeated three times. The second injection was performed 30 minutes after the first injection, and the third injection was performed 210 minutes after that. Experimental animals were divided into five groups according to the time drug administration was initiated. Group I (n = 8) began vehicle administration 30 minutes before occlusion. Group II (n = 9) started 21-aminosteroid administration 30 minutes before occlusion. Drug administration in Group III (n = 9) began at the time of reperfusion, in Group IV (n = 8), 30 minutes after reperfusion, and in Group V (n = 6), 60 minutes after reperfusion. Animals in the control group (n = 5) underwent sham operations. One week after ischemia, the number of viable pyramidal neurons was counted in the hippocampal CA1 subfield. The results were as follows: the number of living neurons in Group I was 18.8 +/- 8.7; in Group II, was 44.7 +/- 9.5; in Group III, was 46.4 +/- 9.4; in Group IV, was 40.3 +/- 6.6; in Group V, was 10.2 +/- 2.5; and in the control group was 131 +/- 3.3. Groups II, III, and IV demonstrated significantly higher numbers of living neurons compared with Group I (P < 0.05). The present study revealed that U-74389G attenuated delayed neuronal death in global cerebral ischemia when it was administered before or soon after the ischemic episode.
一种新型21 - 氨基类固醇（U - 74389G），一种新的强效抗氧化剂，被评估其对短暂性全脑缺血的保护作用。在成年雄性Wistar大鼠中通过四动脉闭塞20分钟诱导缺血。重复三次注射21 - 氨基类固醇（U - 74389G，腹腔注射5mg/kg）。第二次注射在第一次注射后30分钟进行，第三次注射在那之后210分钟进行。根据开始给药的时间将实验动物分为五组。第一组（n = 8）在闭塞前30分钟开始给予赋形剂。第二组（n = 9）在闭塞前30分钟开始给予21 - 氨基类固醇。第三组（n = 9）在再灌注时开始给药，第四组（n = 8）在再灌注后30分钟给药，第五组（n = 6）在再灌注后60分钟给药。对照组（n = 5）的动物接受假手术。缺血一周后，对海马CA1亚区存活的锥体神经元数量进行计数。结果如下：第一组存活神经元数量为18.8±8.7；第二组为44.7±9.5；第三组为46.4±9.4；第四组为40.3±6.6；第五组为10.2±2.5；对照组为131±3.3。与第一组相比，第二、三、四组显示存活神经元数量显著更高（P < 0.05）。本研究表明，当在缺血发作前或发作后不久给予U - 74389G时，它可减轻全脑缺血中的迟发性神经元死亡。
