Low birth weight, uterine infection, and nitric oxide

低出生体重、子宫感染和一氧化氮

基本信息

批准号：
7151219
负责人：
CHANDRASEKHAR YALLAMPALLI
金额：
$ 31.79万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-12-30 至 2008-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7151219
关键词：
Low birth weight uterine infection

项目摘要

Urogenital infections and host factors are often associated with low birth weight, especially in minority populations Most pathogens, including Escherichia coil, develop unique virulence mechanisms to colonize and invade the urogenital tract Bacterial adhesins such as Dr fimbriae of E col interact with host tissue receptors allowing ascending infection and associated complications Nitric oxide (NO), a gaseous molecule with versatile functions including the modulation of infection and immunity, is reported to be produced by uteroplacental tissues The goal of this project is to assess if NO modulates severity of uterine infection through the regulation of bacterial invasion into cells We hypothesize that NO system regulates the uteroplacental bacterial receptor, decay accelerating factor (DAF) and therefore bacterial invasion We propose that this novel mechanism could play a role in severity of infection and perinatal morbidities such as low birth weight These hypotheses will be tested by pursuing three specific aims Specific Aim 1 will determine whether NO inhibits Dr+ E coil attach- ment and internalization into epithelial cells and whether this occurs through suppression of DAF expression Sub-aim 1.1 will characterize NO production, NO synthase (NOS) enzymes in uterine epithelial cell lines, Ishikawa, RL-95 and HEC-1 cells Sub-aim 1.2 will test the hypothesis if manipulation of NO synthesis in these cells, will alter Dr +E coil attachment and internalization Sub-aim 1.3 will test the hypothesis that the epithelial cell DAF protein and mRNA contents are regulated by NO system Specific Aim 2 will establish that modula- tion of NO synthesis in rats will alter severity of infection through the changes in DAF content of the uterus and vasculature in experimental intrauterine infection Sub-aim 2.1 will test the hypothesis that Dr* E coil or group B streptococcus (GBS) infection in uteroplacental tissues is reduced with increases in NO synthesis and is increased with the inhibition of NO synthesis Sub-aim 2.2 will test the hypothesis that changes in DAF content of uteroplacental and vascular tissues are related to chang+es in NO synthesis Specific Aim 3 will examine if inhibition of NO synthesis and experimental intrauterine Dr E coil or GBS infection results in fetal growth restriction in rats, and if so, whether NO donor can reverse the fetal growth restriction Sub-aim 3.1 will test the hypothesis that inhibition of NO synthesis combined with intrauterine Dr+E coil or GBS infection has synergistic detrimental effects on fetal and placental growth Sub aim 3.2 will test the hypothesis that NO donor can reverse the increases in DAF expression in uteroplacental and vascular tissues and in fetal growth restriction

泌尿生殖器感染和宿主因素通常与低出生体重有关，尤其是在少数情况下种群种群大多数病原体，包括埃舍里希亚线圈，都会发展出独特的毒力机制来定居和入侵泌尿生殖道细菌粘附素，例如E col的Fimbriae博士与宿主组织受体相互作用允许升高感染和相关并发症一氧化氮（NO），一种具有多功能的气态分子据报道，包括感染和免疫的调节在内的功能是由子宫结构产生的组织该项目的目的是评估未通过调节调节子宫感染的严重程度细菌侵袭细胞我们假设没有系统调节子宫牙科受体，衰减加速因子（DAF），因此细菌侵袭我们提出这种新型机制可以这些假设将在感染的严重程度和围产期病毒（例如低出生体重）中发挥作用通过追求三个特定目标特定目标1测试将确定no是否抑制DR+ E线圈附件 - 将上皮细胞的内在化和内在化以及是否通过抑制DAF表达发生 Sub-aim 1.1将不表征没有产生，没有子宫上皮细胞系中的合酶（NOS）酶， Ishikawa，RL-95和Hec-1细胞子-AIM 1.2如果在这些中没有合成的情况下，将检验假设细胞将改变Dr +E线圈的附着和内在化子-IAM 1.3将检验上皮的假设细胞DAF蛋白和mRNA含量不受任何系统特异性目标2的调节，将确定调节大鼠无合成的情况将通过子宫DAF含量的变化改变感染的严重程度，实验性宫内感染Sub-Aim 2.1中的脉管系统将检验* e卷或B组的假设子宫类组织中链球菌感染（GBS）的感染随着无合成的增加而减少随着抑制无合成子-AIM 2.2的增加，将检验以下假设：DAF含量的变化子宫牙科和血管组织与chang+es的无合成特定目的3将检查是否会检查是否是否抑制无合成和实验性宫内博士或GBS感染导致胎儿生长大鼠的限制，如果是这样，没有任何捐赠者能否扭转胎儿生长限制子-AIM 3.1将测试假设抑制NO合成与宫内DR+E线圈或GBS感染相结合具有协同作用对胎儿和胎盘生长子的有害影响3.2将检验以下假设：扭转子宫结构和血管组织中DAF表达的增加以及胎儿生长限制