Acute and chronic stress-induced oxidative gastrointestinal mucosal injury in rats and protection by bismuth subsalicylate
Acute and chronic stress-induced oxidative gastrointestinal mucosal injury in rats and protection by bismuth subsalicylate
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DOI：
10.1023/a:1006978431521
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发表时间：
1999-06-01
影响因子：
4.3
通讯作者：
Stohs, SJ
中科院分区：
文献类型：
--
作者：
Bagchi, D;Carryl, OR;Stohs, SJ
活性氧参与应激性胃肠道黏膜损伤的发病机制。在本研究中，我们研究了急性和慢性应激对增强的ROS产生的影响，包括超氧阴离子[SA;通过细胞色素c还原（CCR）]和羟基自由基（OH）测定，并将这些自由基的产生增强与脂质过氧化、膜微粘度和DNA片段化、氧化性组织损伤的指标，在雌性Sprague-Dawley大鼠的胃和肠粘膜中。进一步研究了碱式水杨酸铋（BSS）对急、慢性应激所致胃肠道粘膜损伤的保护作用。急性应激诱导90分钟，而慢性应激诱导15分钟/天，连续15天。暴露于急性应激的一半动物在暴露于急性应激前30分钟口服15 mg BSS/kg进行预处理。同样，一半的动物暴露于水浸束缚慢性应激经口预处理7.5毫克BSS/公斤/天，连续15天前30分钟暴露于慢性应激。与慢性应激相比，急性应激对胃和肠粘膜的损伤更大。急性应激增加CCR和OH生产的10.0和14.3倍，分别在胃粘膜，10.4和17.0倍，分别在肠粘膜。BSS预处理防止了急性应激引起的CCR和OH产生的增加。急性应激使胃粘膜脂质过氧化、DNA断裂和膜微粘度分别增加3.6倍、4.0倍和11.6倍，肠粘膜分别增加4.1倍、5.0倍和16.2倍。BSS减少急性应激引起的脂质过氧化反应，DNA片段化和膜微粘度约26%，35%和30%，分别在胃粘膜和20%，36%和30%，分别在肠粘膜。慢性应激增加CCR和OH生产的4.8倍和6.3倍，分别在胃粘膜，4.6倍和6.9倍，分别在肠粘膜。慢性应激增加脂质过氧化和DNA断裂的2.9倍和3.3倍，分别在胃粘膜和3.3倍和4.2倍，分别在肠粘膜。BSS降低慢性应激引起的脂质过氧化反应，DNA片段化和膜微粘度约41，44和45%，分别在胃粘膜，39，52和51%，分别在肠粘膜。与急性应激相比，每日给予BSS对慢性应激诱导的氧化性胃肠道损伤提供了更大的保护。这些结果表明，急性和慢性应激都可以通过增加ROS的产生诱导胃肠道粘膜损伤，BSS可以显着保护胃肠道粘膜损伤。
Reactive oxygen species (ROS) are implicated in the pathogenesis of stress-induced gastrointestinal mucosal injury. In the present study, we have investigated the effects of acute and chronic stress on the enhanced production of ROS including superoxide anion [SA; as determined by cytochrome c reduction (CCR)] and hydroxyl radicals (OH), and correlated the enhanced production of these free radicals with increased lipid peroxidation, membrane microviscosity and DNA fragmentation, indices of oxidative tissue damage, in the gastric and intestinal mucosa of female Sprague-Dawley rats. Furthermore, the protective ability of bismuth subsalicylate (BSS) against the gastrointestinal mucosal injury induced by acute and chronic stress was determined. Acute stress was induced for a period of 90 min, while chronic stress was induced for 15 min/day for 15 consecutive days. Half of the animals exposed to acute stress were pretreated orally with 15 mg BSS/kg 30 min prior to the exposure to acute stress. Similarly, half of the animals exposed to water-immersion restraint chronic stress were pretreated orally with 7.5 mg BSS/kg/day for 15 consecutive days 30 min prior to the exposure to chronic stress. Acute stress produced greater injury to both gastric and intestinal mucosa as compared to chronic stress. Acute stress increased CCR and OH production by 10.0- and 14.3-fold, respectively, in the gastric mucosa, and 10.4- and 17.0-fold, respectively, in the intestinal mucosa. Pretreatment with BSS prevented the acute stress-induced increase in CCR and OH production. Acute stress increased lipid peroxidation, DNA fragmentation and membrane microviscosity by 3.6-, 4.0- and 11.6-fold, respectively, in gastric mucosa, and 4.1-, 5.0- and 16.2-fold, respectively, in intestinal mucosa. BSS decreased acute stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by approximately 26, 35 and 30%, respectively, in gastric mucosa, and by 20, 36 and 30%, respectively, in the intestinal mucosa. Chronic stress increased CCR and OH production by 4.8- and 6.3-fold, respectively, in gastric mucosa, and 4.6- and 6.9-fold, respectively, in intestinal mucosa. Chronic stress increased lipid peroxidation and DNA fragmentation by 2.9- and 3.3-fold, respectively, in gastric mucosa, and 3.3- and 4.2-fold, respectively, in intestinal mucosa. BSS decreased chronic stress-induced lipid peroxidation, DNA fragmentation and membrane microviscosity by approximately 41, 44 and 45%, respectively, in gastric mucosa, and by 39, 52 and 51%, respectively, in the intestinal mucosa. Daily administration of BSS provided greater protection against chronic stress-induced oxidative gastrointestinal injury as compared to the acute stress. These results demonstrate that both acute and chronic stress can induce gastrointestinal mucosal injury through enhanced production of ROS, and that BSS can significantly protect against gastrointestinal mucosal injury.