NOX, a novel nitric oxide scavenger, reduces bacterial translocation in rats after endotoxin challenge
NOX, a novel nitric oxide scavenger, reduces bacterial translocation in rats after endotoxin challenge
复制标题
DOI：
10.1152/ajpgi.1999.277.6.g1281
复制
发表时间：
1999-12-01
影响因子：
4.5
通讯作者：
Ford, H
中科院分区：
文献类型：
--
作者：
Dickinson, E;Tuncer, R;Ford, H
内毒素血症通过上调肠道中的诱导型一氧化氮合酶（iNOS）促进肠道屏障衰竭和细菌移位（BT）。我们假设，管理的二硫代氨基甲酸酯衍生物，NOX，清除一氧化氮（NO），可能会减少肠损伤和BT后脂多糖（LPS）的挑战。将Sprague-Dawley大鼠在LPS攻击之前或之后通过皮下放置的渗透泵随机接受NOX或生理盐水。24小时后培养肠系膜淋巴结、肝、脾和血液。在Ussing室中测量大肠杆菌C-25或荧光珠的荧光传代。肠细胞凋亡，诱导型一氧化氮合酶的表达，和硝基酪氨酸免疫反应性进行了形态学检查。NOX显着降低了菌血症，BT，和细菌和珠的经粘膜通道的发生率，当给药前或LPS攻击后12小时。LPS诱导肠上皮细胞凋亡的绒毛提示，其中细菌进入共聚焦显微镜证实。NOX显著减少凋亡细胞核和硝基酪氨酸残基的数量。NOX通过清除NO及其毒性衍生物过氧亚硝酸盐来预防LPS诱导的肠道屏障功能衰竭。
Endotoxemia promotes gut barrier failure and bacterial translocation (BT) by upregulating inducible nitric oxide synthase (iNOS) in the gut. We hypothesized that administration of a dithiocarbamate derivative, NOX, which scavenges nitric oxide (NO), may reduce intestinal injury and BT after lipopolysaccharide (LPS) challenge. Sprague-Dawley rats were randomized to receive NOX or normal saline via subcutaneously placed osmotic pumps before or after LPS challenge. Mesenteric lymph nodes, liver, spleen, and blood were cultured 24 h later. Transmucosal passage of Escherichia coli C-25 or fluorescent beads were measured in an Ussing chamber. Intestinal membranes were examined morphologically for apoptosis, iNOS expression, and nitrotyrosine immunoreactivity. NOX significantly reduced the incidence of bacteremia, BT, and transmucosal passage of bacteria and beads when administered before or up to 12 h after LPS challenge. LPS induced enterocyte apoptosis at the villus tips where bacterial entry was demonstrated by confocal microscopy. NOX significantly decreased the number of apoptotic nuclei and nitrotyrosine residues. NOX prevents LPS-induced gut barrier failure by scavenging NO and its toxic derivative, peroxynitrite.