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。这个 据报道，糖尿病患者的死亡率最高(10- 15%)和以下发展为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 占每例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，因此不能接受药物治疗 时间到了。 花生四烯酸的代谢物涉及到所有领域的 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、胆囊壁收缩 和胆结石的形成。这项建议的具体目标是： A)描述急性炎症性疾病的关系 动物胆囊二十聚糖体的改变与胆囊症 生产；b)这些变化对体外水的影响 运输，以及c)确定入侵巨噬细胞的作用 和成纤维细胞中发现的胆囊二十多糖的变化 制作。这种方法将定义生物化学变化在 亚细胞膜组分中花生四烯酸的代谢 和整个组织的炎症反应和影响 前列腺素和白三烯产生的特异性抑制剂 这些变化。二十烷类化合物将由 放射层析与反相高压液体 层析和放射免疫分析。侵袭巨噬细胞的作用和 成纤维细胞作为二十烷类化合物产生变化的来源将 通过细胞培养、光和透射电子来研究 显微镜。二十烷基类物质的产生会使炎症细胞 用放射免疫法和层析法进行分析 上面提到的技术。 这些研究的长期目标有两个方面。第一，要 确定胆道梗阻导致移行的原因 炎症细胞与花生四烯酸的释放 急性胆囊炎早期的代谢物。第二，到 制定治疗策略，预防或减轻艾滋病的影响 这些早期事件。

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.