Compartmental analysis of proteomic biomarkers during intra-uterine infections

子宫内感染期间蛋白质组生物标志物的区室分析

基本信息

批准号：
7799992
负责人：
Peta Louise Grigsby
金额：
$ 24.9万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-13 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7799992
关键词：
ANXA2 gene Address Amniotic Fluid Animals Anti-Inflammatory Agents Anti-inflammatory Antibiotic Therapy Antibiotics Arteries Award Bacteria Bacterial Vaginosis Biological Assay Biological Markers Blood Brain Injuries Calgranulin B Cardiovascular system Catheters Cells Cervical Cesarean section Characteristics Chorion Clinical Control Groups Data Detection Diagnosis Diagnostic Dinoprostone Disease Progression Dose Early Diagnosis Electrodes Endocrine Experimental Models Femoral vein Fetal Lung Fetal Membranes Fetal Tissues Fetus Functional disorder Genital system Gestational Age Growth Hour IL8 gene Immunoassay Implant In Situ Hybridization In Vitro Individual Infection Inflammation Inflammatory Inflammatory Response Infusion procedures Insulin-Like Growth-Factor Binding Protein 1 Interleukin-6 Invaded Laboratories Length Leukocytes Link Macaca mulatta Matrix Metalloproteinases Measurement Membrane Mentors Methodology Methods Microbe Modeling Molecular Profiling Monitor Monkeys Mycoplasma Neonatal Operative Surgical Procedures Palpation Pan Genus Phase Physiological Adaptation Plasma Postoperative Care Pregnancy Premature Birth Premature Labor Procedures Process Production Property Proteins Proteomics Protocols documentation Research Design Research Proposals Resolution Saline Sampling Schedule Simulate Source Staging Sterility Stimulus System Techniques Therapeutic Therapeutic Intervention Tissues Ultrasonography Umbilical Cord Blood Ureaplasma Ureaplasma urealyticum biovar 1 Western Blotting amnion amniotic cavity cytokine fetal fetal blood genital infection hemodynamics implantation intraamniotic infection microorganism myometrium nonhuman primate novel novel strategies premature prevent prognostic indicator respiratory response uterine contractility vaginal fluid

项目摘要

The objectives of this research proposal are to characterize the mechanistic and temporal relationships among biomarker expression profiles (e.g., IGFBP-1 proteolytic fragments, calgranulin B and annexin II) in maternal and fetal compartments during defined stages of ascending infection with genital mycoplasmas (from choriodecidual to intra-amniotic models). It is our hypothesis that spatial and temporal characteristics of specific proteomic biomarkers in cervical vaginal fluid (CVF), amniotic fluid, maternal and fetal blood, will act as surrogates for the stage of progression of intra-uterine infection; similarly, changes in biomarker expression profiles during maternal therapeutic interventions (antibiotic and anti-inflammatory agents), will serve as prognostic indicators. Fetal physiological adaptations (i.e., cardiovascular hemodynamics, respiratory parameters,endocrine status) will be assessed in early and advanced stages of infection, and in response to maternal antibiotic therapy. Complemetary in vitro studies will assess the ability of U. parvum to invade and transcytose through intact chorioamniotic membranes and gain entry into the amniotic cavity. The production rates of specific biomarkers and the secretory profiles of IL-1B, TNF-a, IL-6 and IL-8 by component tissue layers will illuminate the tissue source of specific biomarker profiles observed in the amniotic fluid and cervical vaginal fluid (CVF) during intra-uterine infection. Moreover, these studies will provide important information on the contribution of the amnion or choriodecidua to the inflammatory response following U. parvum exposure. A number of specific endpoints will be ascertained that will aid in our understanding of causal links among choriodecidual colonization with U. parvum and the biologic and clinical manifestations of early and late stages of ascending uterine infection. Uterine contractility, serial assesment of cervical length (by ultrasound and palpation), amniotic fluid levels of PGE2, PGF2a, cytokines, leukocytes and MMPs will be correlated with biomarker expression profiles in the CVF, amniotic fluid and maternal and fetal blood. Quantitative cultures and PCR for ureaplasmas will be performed on amniotic fluid, blood and fetal tissues.

本研究计划的目的是表征在生殖器支原体（来自绒毛膜蜕膜组织）上行感染的特定阶段，母体和胎儿区室中生物标志物表达谱（例如 IGFBP-1 蛋白水解片段、钙粒蛋白 B 和膜联蛋白 II）之间的机制和时间关系。羊膜内模型）。我们的假设是，宫颈阴道液（CVF）、羊水、母体和胎儿血液中特定蛋白质组生物标志物的空间和时间特征将作为宫内感染进展阶段的替代指标；同样，母亲治疗干预（抗生素和抗炎药物）期间生物标志物表达谱的变化将作为预后指标。将在感染的早期和晚期以及对母体抗生素治疗的反应中评估胎儿的生理适应（即心血管血流动力学、呼吸参数、内分泌状态）。补充性体外研究将评估小 U. parvum 侵入完整绒毛膜羊膜并转胞吞并进入羊膜腔的能力。特定生物标志物的产生率以及各组织层的 IL-1B、TNF-a、IL-6 和 IL-8 的分泌谱将阐明在羊水和宫颈阴道液 (CVF) 中观察到的特定生物标志物谱的组织来源）在宫内感染期间。此外，这些研究将提供有关羊膜或脉络膜蜕膜对接触小 U. parvum 后炎症反应的重要信息。将确定一些具体的终点，这将有助于我们了解小 U. parvum 的绒毛膜蜕膜定植与上行子宫感染早期和晚期的生物学和临床表现之间的因果关系。子宫收缩力、宫颈长度的连续评估（通过超声和触诊）、羊水中 PGE2、PGF2a、细胞因子、白细胞和 MMP 的水平将与 CVF、羊水以及母体和胎儿血液中的生物标志物表达谱相关。将对羊水、血液和胎儿组织进行解脲脲原体定量培养和 PCR。