PATHOGENESIS AND TREATMENT OF EXPERIMENTAL PERITONITIS

描述：（改编自申请人摘要）细菌 易位（BT）被定义为微生物从 肠腔到宿主的任何腔外部位。 一些BT可能是 正常 然而，各种压力夸大了BT，并有助于 全身性感染的发病机制。 初步数据显示， 肠上皮细胞产生的蛋白质可能在肠上皮细胞的发病机制中起调节作用。 夸张的BT 在某些病理条件下，NO的过度产生可能 诱导细胞损伤并导致肠上皮细胞凋亡， 屏障失效和BT增加。 这项研究的目的是确定 NO在体内和体外调节BT的机制。 该研究 三个具体目标：I）研究NOS-2在 肠道受到各种因素的影响，包括细胞因子、腔内容物和 上皮内淋巴细胞; II）使用NOS-2敲除小鼠测定 和NOS-2基因转移实验，NO调节的机制， III）为了确定各种细菌的作用， 活性氮（RNI）对BT的影响。

DESCRIPTION: (Adapted from the applicant's abstract) Bacterial translocation (BT) is defined as the transfer of microbes from the intestinal lumen to any extra-luminal site in the host. Some BT is probably normal. However, a variety of stresses exaggerate BT and contribute to the pathogenesis of systemic infections. Preliminary data suggest that NO production by enterocytes may play a regulatory role in the pathogenesis of exaggerated BT. In certain pathologic conditions, overproduction of NO may induce cellular injury and lead to enterocyte apoptosis resulting in gut barrier failure and increased BT. The goal of the study is to determine the mechanisms by which NO regulates BT in vivo and in vitro. The study has three specific aims: I) to study the regulation of NOS-2 within the intestine by various factors, including cytokines, luminal contents, and intra-epithelial lymphocytes; II) to determine, using NOS-2 knockout mice and NOS-2 gene-transfer experiments, the mechanisms by which NO regulates transmucosal passage of bacteria; III) to determine the effect of various reactive nitrogen species (RNI) on BT.