ROLE OF SPLANCHNIC EICOSANOIDS DURING SHOCK

内脏类二十烷酸在休克期间的作用

• 批准号: 6107531
• 负责人: STUART I MYERS
• 金额: --
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107531
• 关键词: eicosanoid metabolism; free radical oxygen; gastrointestinal absorption /transport; gastrointestinal circulation; gastrointestinal infection; gastrointestinal motility /pressure; hemorrhagic shock; laboratory rat; morphine; multiple organ failure; nitric oxide; oxidative stress; physiologic stressor; platelets; reperfusion; septic shock; serotonin; vasoconstriction

Multiple organ failure (MOF) is a serious, often fatal sequelae of visceral ischemia, resuscitation after severe hemorrhage, sepsis, or following traumatic injury. The overall long term goal of this proposal is to elucidate the humoral factors that contribute to the regulation of splanchnic blood flow during hemorrhage/reperfusion injury. The endogenous humoral factors that contribute to splanchnic blood flow that will be studied include vasoactive eicosanoids and nitric oxide (NO). The exogenous humoral factors investigated include platelet derived vasoconstrictors and oxygen-derived free radicals (ODFRs) formed during hemorrhage/reperfusion injury. Our long term goal is to investigate the specific mechanisms involved in the regulation of the enzymes responsible for eicosanoid and nitric oxide synthesis and degradation during shock states which will contribute to the development of treatment strategies designed to maintain splanchnic blood flow and visceral function following shock. Acute hemorrhage followed by reperfusion will be used either as a primary injury or as an initial injury followed by a second insult to examine the following specific aims: 1) To determine the role of ODFRs on splanchnic eicosanoid synthesis and NO synthesis following early hemorrhagic shock and reperfusion; 2) to determine the role of ODFR on the regulation of splanchnic blood flow following hemorrhagic shock and reperfusion; 3) To determine the role of local platelet eicosanoid and serotonin release in the splanchnic vascular bed following hemorrhagic shock and reperfusion; 4) To determine the role of a second trauma (endotoxin shock, hemorrhage) on splanchnic eicosanoid and NO synthesis and splanchnic blood flow following initial hemorrhagic shock. This proposal will utilize several strategies to determine the role of ODFRs on splanchnic eicosanoid and NO synthesis and splanchnic blood flow during shock. The first strategy will examine the effects of hemorrhage/reperfusion injury on splanchnic eicosanoid and nitric oxide synthesis and release. These studies will determine the location and molecular mechanisms involved with the regulation of the enzymes responsible for splanchnic eicosanoid and nitric oxide synthesis during hemorrhage/reperfusion injury. The second strategy is to examine the effects of ODFRs on splanchnic blood flow following hemorrhage/reperfusion injury. The third strategy is to examine the contribution of platelets to splanchnic vasoconstriction during hemorrhage/reperfusion by release of serotonin and thromboxane. The fourth strategy is to determine the effect of a second trauma (hemorrhage, endotoxin, morphine etc.) on the splanchnic eicosanoid and nitric oxide synthesis and splanchnic blood flow following initial hemorrhage.

多器官衰竭（MOF）是一种严重的，往往是致命的后遗症， 内脏缺血，严重出血后复苏，败血症，或 创伤性损伤后。 本提案的总体长期目标 是阐明体液因素，有助于调节 出血/再灌注损伤时内脏血流量。 的 内源性体液因子，有助于内脏血流量， 包括血管活性类花生酸和一氧化氮（NO）。 研究的外源性体液因子包括血小板衍生的 血管收缩剂和氧衍生自由基（ODFRs）形成的过程中， 出血/再灌注损伤。 我们的长期目标是调查 参与调节酶的特定机制 在休克期间类花生酸和一氧化氮的合成和降解 有助于制定治疗战略的国家 旨在维持内脏血流量和内脏功能 休克后。 急性出血后再灌注将被用作原发性 伤害或作为第一次伤害，然后是第二次侮辱，以检查 1）确定ODFRs对内脏器官的作用， 失血性休克早期类花生酸合成和NO合成 2）探讨ODFR对缺血再灌注损伤的调节作用。 失血性休克和再灌注后内脏血流量; 3） 确定局部血小板类花生酸和5-羟色胺释放在 失血性休克再灌注后内脏血管床; 4)确定二次创伤（内毒素休克、出血）的作用 对内脏类花生酸和NO合成及内脏血流量的影响 在最初的失血性休克之后 本提案将利用若干战略来确定以下方面的作用： 内脏类花生酸和NO合成与内脏血流量的ODFRs 在休克期间。 第一项战略将研究 失血/再灌注损伤对内脏类花生酸和一氧化氮影响 合成和释放。 这些研究将确定地点， 参与酶调节的分子机制 负责内脏类花生酸和一氧化氮的合成， 出血/再灌注损伤。 第二个策略是检查 ODFRs对内脏血流量的影响 出血/再灌注损伤。 第三个策略是检查 血小板对内脏血管收缩的作用 通过释放5-羟色胺和血栓素引起的出血/再灌注。 的 第四种策略是确定第二次创伤的影响 （出血、内毒素、吗啡等）内脏类花生酸， 一氧化氮合成和内脏血流量 出血