Megison S M, Horton J W, Chao H, Walker P B
Department of Surgery, University of Texas Southwest Medical Center, Dallas 75235-9031.
Circ Shock. 1990 Apr;30(4):323-9.
Studies demonstrating protective effects of allopurinol in intestinal ischemia have been carried out using i.v. allopurinol (presently unavailable for human use) or enteral allopurinol at supra-normal doses and, therefore, have questionable clinical relevance. We evaluated the protective effects of clinically used doses of enteral allopurinol in rats with intestinal ischemia. One hundred nine male Sprague-Dawley rats (250-300 gm) received enteral allopurinol (5-30 mg/kg) or water daily for 1 week and were subjected to superior mesenteric artery occlusion for 20, 30, or 45 min. Mortality in water-fed controls after 20 min of mesenteric ischemia was 50%, but there was no mortality in rats pretreated with allopurinol (5, 10, and 20 mg/kg/day) in this group (P = 0.016). There was no reduction in mortality after allopurinol pretreatment at any dose in rats with 30 or 45 min of ischemia. We concluded that 1) prolonged intestinal ischemia causes lethal damage during the hypoperfusion phase that cannot be prevented by allopurinol pretreatment even at supra-normal doses, and 2) allopurinol at recommended enteral doses (5-10 mg/kg/day) can reduce morality from reperfusion injury when the phase of hypoperfusion is not, in itself, lethal. Allopurinol is effective in reducing reperfusion injury in the currently available enteral form in dose ranges that should not cause prohibitive side effects.
已开展的研究显示别嘌醇对肠道缺血具有保护作用，这些研究使用的是静脉注射别嘌醇（目前无法用于人类）或超正常剂量的肠内别嘌醇，因此其临床相关性存疑。我们评估了临床使用剂量的肠内别嘌醇对肠道缺血大鼠的保护作用。109只雄性Sprague-Dawley大鼠（体重250 - 300克）每天接受肠内别嘌醇（5 - 30毫克/千克）或水，持续1周，然后进行肠系膜上动脉闭塞20、30或45分钟。肠系膜缺血20分钟后，喂水对照组的死亡率为50%，但该组中用别嘌醇（5、10和20毫克/千克/天）预处理的大鼠无死亡（P = 0.016）。在缺血30或45分钟的大鼠中，任何剂量的别嘌醇预处理后死亡率均未降低。我们得出结论：1）长时间的肠道缺血在低灌注期会造成致命损伤，即使使用超正常剂量的别嘌醇预处理也无法预防；2）当低灌注期本身不致命时，推荐的肠内剂量（5 - 10毫克/千克/天）的别嘌醇可降低再灌注损伤导致的死亡率。别嘌醇以目前可用的肠内剂型在不会引起严重副作用的剂量范围内有效降低再灌注损伤。
