SURGICAL STUDIES ON GALLBLADDER INFLAMMATION

急性胆囊炎（胆囊炎）是严重的 可导致大量发病和死亡的疾病。 的 据报道，糖尿病患者的死亡率最高（10- 15%）和发生非结石性胆囊炎的患者， 创伤或败血症（40-70%）。 急性非结石性胆囊炎 占500，000例胆囊切除术的4-8%， 年 急性胆囊炎的确切机制是 不为人所知，因此不适合医学治疗， 时间 花生四烯酸代谢物涉及所有领域， 动物胆囊生理学的体外研究。 这些研究 包括水运输、粘蛋白产生、胆囊收缩 和胆结石形成。 这项建议的具体目标是： a）描述急性炎症与 动物胆囊类花生酸改变 B）这些变化对体外水的影响 运输，以及c）确定侵入巨噬细胞的作用 和成纤维细胞在胆囊类花生酸变化中的作用 生产 这种方法将定义生物化学的变化， 亚细胞膜组分中花生四烯酸代谢 和整个组织诱导的炎症和影响， 前列腺素和白三烯产生的特异性抑制剂， 这些变化。 将通过以下方法分析类二十烷酸： 放射色谱法和反相高压液相色谱法 层析和RIA。 侵袭性巨噬细胞的作用， 成纤维细胞作为类花生酸产生变化的来源， 通过细胞培养、光和透射电子 显微镜 炎症细胞产生类花生酸 通过放射免疫分析和色谱分析 上述技术。 这些研究的长期目标有两个方面。 一是 确定为什么胆道梗阻会导致 炎症细胞和花生四烯酸的释放 急性胆囊炎的早期症状 二是 制定治疗策略，以防止或减轻 这些早期的事件。

Acute inflammation of the gallbladder (cholecystitis) is a serious disease which can cause substantial morbidity and death. The most significant mortality is reported in diabetic patients (10- 15%) and in patients developing acalculous cholecystitis following trauma or sepsis (40-70%). Acute acalculous cholecystitis represents 4-8% of the 500,000 cholecystectomies performed each year. The exact mechanism of acute gallbladder inflammation is not well known and thus not amenable to medical therapy a this time. Arachidonic acid metabolites have been implicated in all areas of animal gallbladder physiology by in vitro studies. These studies include water transport, mucin production, gallbladder contraction and gallstone formation. The specific aims of this proposal are: a) to delineate the relationship of acute inflammation of the gallbladder with alterations in animal gallbladder eicosanoid production; b) the effect of these changes on in vitro water transport, and c) to determine the role of invading macrophages and fibroblasts in the changes found in gallbladder eicosanoid production. This approach will define the biochemical changes in arachidonic acid metabolism in subcellular membrane fractions and whole tissue induced by inflammation and the effect of specific inhibitors of prostaglandin and leukotriene production on these changes. Eicosanoids will be analyzed by radiochromatography and reversed phase high pressure liquid chromatography and RIA. The role of invading macrophages and fibroblasts as the source for changes in eicosanoid production will be studied by cell culture and light and transmission electron microscopy. Eicosanoid production of the inflammatory cells will be analyzed by radioimmunoassay and the chromatography techniques mentioned above. The long term goals of these studies are two fold. First, to determine why biliary obstruction leads to in-migration of inflammatory cells and the release of arachidonic acid metabolites in the early stages of acute cholecystitis. Second, to establish treatment stratagies to prevent or lessen the impact of these early events.