XANTHINE-OXIDASE AND NEUTROPHIL INFILTRATION IN INTESTINAL ISCHEMIA
XANTHINE-OXIDASE AND NEUTROPHIL INFILTRATION IN INTESTINAL ISCHEMIA
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DOI：
10.1152/ajpgi.1986.251.4.g567
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发表时间：
1986-10-01
影响因子：
--
通讯作者：
GRANGER, DN
中科院分区：
文献类型：
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作者：
GRISHAM, MB;HERNANDEZ, LA;GRANGER, DN
越来越多的实验数据表明，超氧化物、过氧化氢和羟自由基等活性氧代谢物可能介导缺血性肠再灌注引起的粘膜损伤。黄嘌呤氧化酶被认为是这些还原性 O2 物质的主要来源，因为用别嘌呤醇或蝶呤醛等黄嘌呤氧化酶抑制剂进行预处理可以预防缺血后粘膜损伤。氧自由基的另一个潜在来源是炎症性中性粒细胞。为了确定中性粒细胞是否在小肠缺血再灌注损伤的发病机制中发挥作用，我们检查了缺血和再灌注对中性粒细胞浸润以及还原型谷胱甘肽、超氧化物歧化酶和过氧化氢酶的组织水平的影响。我们的研究表明，缺血肠道的再灌注会导致中性粒细胞浸润急剧增加 (1,800%)，同时还原型谷胱甘肽和超氧化物歧化酶分别损失 60% 和 30%。过氧化氢酶活性不受缺血再灌注的影响。用别嘌呤醇预处理或施用超氧化物歧化酶可防止中性粒细胞的流入并延缓还原型谷胱甘肽水平的下降。这些结果表明黄嘌呤氧化酶产生的氧自由基、中性粒细胞外渗和粘膜损伤之间存在关系。我们认为，缺血和再灌注导致黄嘌呤氧化酶产生的、超氧化物依赖性炎症中性粒细胞在粘膜中积聚，其中中性粒细胞衍生的活性氧代谢物介导和/或加剧肠道损伤。
A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radical may mediate the mucosal injury produced by reperfusion of ischemic intestine. Xanthine oxidase has been proposed as the primary source of these reduced O2 species because pretreatment with xanthine oxidase inhibitors such as allopurinol or pterin aldehyde prevent postischemic mucosal injury. Another potential source of oxygen radicals is the inflammatory neutrophil. To ascertain whether neutrophils could play a role in the pathogenesis of ischemia-reperfusion injury in the small bowel we examined the effect of ischemia and reperfusion on neutrophil infiltration and tissue levels of reduced glutathione, superoxide dismutase, and catalase. Our studies demonstrate that reperfusion of ischemic intestines results in a dramatic increase (1,800%) in neutrophil infiltration and a concurrent loss of reduced glutathione and superoxide dismutase of 60 and 30%, respectively. Catalase activity was unaffected by ischemia-reperfusion. Pretreatment with allopurinol or administration of superoxide dismutase prevented the influx of neutrophils and retarded the drop in reduced glutathione levels. These results suggest a relationship among xanthine oxidase-generated oxy radicals, neutrophil extravasation, and mucosal damage. We propose that ischemia and reperfusion results in xanthine oxidase-generated, superoxide-dependent accumulation of inflammatory neutrophils in the mucosa where neutrophil-derived reactive oxygen metabolites mediate and/or exacerbate intestinal injury.