Ishii M, Shimizu S, Nawata S, Kiuchi Y, Yamamoto T
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Dig Dis Sci. 2000 Jan;45(1):93-8. doi: 10.1023/a:1005413511320.
The purpose of this study was to examine whether tetrahydrobiopterin (BH4), a cofactor of nitric oxide (NO) synthase, attenuates gastric ischemia-reperfusion injury induced by clamping of the celiac artery. Gastric injury was assessed by a formation of gastric mucosal erosions. The gastric injury was observed at 30 and 60 min after reperfusion following 30-min ischemia and was reduced by superoxide dismutase (SOD), catalase, or NO synthase inhibitors. Therefore, reactive oxygen species (ROS) and NO seem to be implicated in the ischemia-reperfusion injury. Treatment with BH4 reduced the ischemia-reperfusion injury. Pretreatment with sepiapterin, a precursor of BH4, also reduced the ischemia-reperfusion injury with an increase in BH4 content in serum and stomach. Both the increase in BH4 content and the protective effect of sepiapterin were prevented of pretreatment with N-acetylserotonin, an inhibitor of BH4 synthesis. These results suggest that the increase in BH4 content may protect against gastric ischemia-reperfusion injury via reduction of ROS and/or NO toxicity. BH4 might be useful as a therapeutic agent for gastric ischemia-reperfusion injury.
本研究的目的是检测一氧化氮（NO）合酶的辅助因子四氢生物蝶呤（BH4）是否能减轻由腹腔动脉夹闭诱导的胃缺血-再灌注损伤。通过胃黏膜糜烂的形成来评估胃损伤。在30分钟缺血后再灌注30分钟和60分钟时观察到胃损伤，超氧化物歧化酶（SOD）、过氧化氢酶或NO合酶抑制剂可减轻这种损伤。因此，活性氧（ROS）和NO似乎与缺血-再灌注损伤有关。BH4治疗可减轻缺血-再灌注损伤。用BH4的前体蝶酰三谷氨酸预处理也可减轻缺血-再灌注损伤，同时血清和胃中BH4含量增加。BH4合成抑制剂N-乙酰血清素预处理可阻止BH4含量的增加和蝶酰三谷氨酸的保护作用。这些结果表明，BH4含量的增加可能通过降低ROS和/或NO毒性来预防胃缺血-再灌注损伤。BH4可能作为胃缺血-再灌注损伤的治疗药物。
