SURGICAL STUDIES ON GALLBLADDER INFLAMMATION

急性胆囊炎是一种常见疾病，可导致相当高的发病率。 和死亡。目前对急性胆囊炎的明确治疗仍在继续 外科手术，内科治疗只用于稳定病人 在做胆囊切除术之前。这个项目的总体长期目标是 建议是描绘出一系列复杂的刺激机制 局部胆囊成纤维细胞在治疗过程中增加二十烷类化合物的释放 引发急性胆囊炎。我们的长期目标是建立 抑制释放的特定二十烷类化合物的药物治疗方案 通过刺激胆囊成纤维细胞预防或延缓胆汁淤积 引发急性胆囊炎。 兔胆总管结扎(BDL，急性胆囊炎模型) 用来检查以下具体目标：1)确定 营养因子(胆汁脂类改变、胆囊腔内增多 压力)参与了对胆囊二十烷类物质的调节 急性炎症进展过程中的合成；2)确定 调节细胞合成和释放增加的分子机制 胆汁淤积症后的胆囊二十烷类物质；3)测定细胞内 促进酶“上调”的途径 负责72小时BDL培养中PGI2的增加。 该提案将利用几种战略来确定 急性胆囊炎发病过程中的胆囊型二十烷基硫酸酯。这个 第一种策略将研究胆囊腔内增多的影响。 压力和胆脂变化对胆囊粘膜组织学和胆汁动力学的影响 二十烷醇类药物的释放。第二种策略将研究分子 胆囊环二十烷合成增加的机制和 在早期胆囊炎开始时释放。第三个战略 将研究细胞内第二信使在细胞内的作用 刺激二十烷类化合物合成的酶的调节 在急性胆囊炎的发病和传播过程中。

Acute cholecystitis is a common disease that causes substantial morbidity and death. Current definitive treatment of acute cholecystitis continues to be surgical with medical treatment utilized only to stabilize patients prior to cholecystectomy. The overall long term objective of this proposal is to delineate the complex series of mechanisms that stimulate local gallbladder fibroblasts to increase eicosanoid release during the initiation of acute cholecystitis. Our long term goal is to establish medical treatment regimens that inhibit the specific eicosanoids released by the stimulated gallbladder fibroblasts to prevent or retard the initiation of acute cholecystitis. Rabbit common bile duct ligation (BDL, model of acute cholecystitis) will be utilized to examine the following specific aims: 1) To determine the trophic factors (altered biliary lipids, increased intra-gallbladder pressure) involved with the regulation of gallbladder eicosanoid synthesis during evolving acute inflammation; 2) To determine the molecular mechanisms regulating the increase synthesis and release of gallbladder eicosanoid following BDL; 3) To determine the intracellular pathways that contribute to the "up regulation" of the enzymes responsible for increased PGI2 in the 72-hour BDL cultures. The proposal will utilize several strategies to determine the role of gallbladder eicosanoids in the initiation of acute cholecystitis. The first strategy will examine the effects of increased intra-gallbladder pressure and altered biliary lipids on gallbladder mucosal histology and eicosanoid release. The second strategy will examine the molecular mechanisms responsible for increased gallbladder eicosanoid synthesis and release during the initiation of early cholecystitis. The third strategy will be to examine the role of intracellular second messengers on the regulation of the enzymes responsible for stimulated eicosanoid synthesis during the initiation and propagation of acute cholecystitis.