Megison S M, Horton J W, Chao H, Walker P B
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9031.
J Pediatr Surg. 1990 Aug;25(8):917-21. doi: 10.1016/0022-3468(90)90204-m.
Previous studies demonstrating protective effects of allopurinol in intestinal ischemia have evaluated intravenous allopurinol (presently unavailable for human use) or enteral allopurinol at supranormal doses and, therefore, have questionable clinical relevance. To address this problem, we evaluated the protective effects of clinically used doses of enteral allopurinol in rats with intestinal ischemia. Forty male Sprague-Dawley rats (weighing 300 to 400 g) received enteral allopurinol (10 mg/kg) or water daily for 1 week. Rats were then subjected to superior mesenteric artery occlusion with interruption of collateral flow for 20 minutes to produce ischemic injury to the intestine. Segmental small bowel resections were performed in 10 control rats and 10 allopurinol-treated rats before and after reperfusion to identify histopathologic evidence of reperfusion injury. Mucosal injury was quantitated using a grading scale of 0 to 5 (5 being most severe). The remaining 20 rats (10 in each group) were observed for mortality (death within 7 days) after reperfusion. Mucosal injury after reperfusion was graded at 4.4 +/- 0.20 in controls versus 2.3 +/- 0.23 in the treated group (P less than .001). In addition, there was a significant increase in mucosal damage in the control group when postreperfusion specimens were compared with specimens taken before reperfusion (2.8 +/- 0.19 before and 4.4 +/- 0.20 after reperfusion, P less than .001). Injury score for the allopurinol-treated group did not significantly increase after reperfusion. Survival was 50% in the water-fed control group compared with 100% survival in allopurinol-treated rats (P = .016). We conclude that enteral allopurinol in the presently available form and dose is effective in reducing mesenteric reperfusion injury.
以往关于别嘌醇对肠缺血具有保护作用的研究，评估的是静脉注射用别嘌醇（目前尚未用于人体）或超生理剂量的肠内别嘌醇，因此其临床相关性存疑。为解决这一问题，我们评估了临床常用剂量的肠内别嘌醇对肠缺血大鼠的保护作用。40只雄性Sprague-Dawley大鼠（体重300至400克）每天接受肠内别嘌醇（10毫克/千克）或水，持续1周。然后对大鼠进行肠系膜上动脉闭塞并阻断侧支血流20分钟，以造成肠道缺血性损伤。在10只对照大鼠和10只别嘌醇治疗的大鼠再灌注前后进行节段性小肠切除术，以确定再灌注损伤的组织病理学证据。使用0至5级评分量表（5级为最严重）对黏膜损伤进行定量。其余20只大鼠（每组10只）在再灌注后观察死亡率（7天内死亡）。再灌注后对照组的黏膜损伤评分为4.4±0.20，而治疗组为2.3±0.23（P＜0.001）。此外，与再灌注前采集的标本相比，对照组再灌注后黏膜损伤显著增加（再灌注前为2.8±0.19，再灌注后为4.4±0.20，P＜0.001）。别嘌醇治疗组的损伤评分在再灌注后没有显著增加。饮水对照组的存活率为50%，而别嘌醇治疗的大鼠存活率为100%（P = 0.016）。我们得出结论，目前可用剂型和剂量的肠内别嘌醇可有效减轻肠系膜再灌注损伤。
