PREMATURE LABOR, ENDOTOXEMIA AND CYTOKINE MECHANISMS

早产、内毒素血症和细胞因子机制

• 批准号: 3087086
• 负责人: SCOTT SNYDER
• 金额: $ 7.83万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087086
• 关键词: Escherichia coli infections; calcium; cytokine; cytokine receptors; decidua; endometrium; endotoxins; gestational age; immunomodulators; inhibitor /antagonist; interleukin 1; laboratory rat; muscle contraction; myometrium; oxytocin; platelet activating factor; pregnancy; pregnancy infection; premature labor; prostaglandin F; prostaglandin endoperoxide synthase; smooth muscle; statistics /biometry; stimulant /agonist; tumor necrosis factor alpha; uterus

The single greatest cause of mortality and morbidity in newborn infants is premature birth. Although the pathogenic factors responsible for preterm parturition are unknown, recent studies indicate that endotoxin from bacterial infection can provoke the release of tumor necrosis factor (TNFalpha), interleukin 1 (IL-1beta), and platelet activating factor (PAF) from the decidua and are then projected to cause premature labor through some unknown mechanism. We propose to test two hypotheses: that TNFalpha, IL-1beta and PAF directly alter myometrial contractile function and that endotoxemia alters uterine contractile characteristics. Contractile effects of TNFalpha, IL-1beta and PAF will be examined singly and in combination with known agonists in uterine effects of TNFalpha, PAF and IL-1beta are altered by known receptor antagonists, determine if gestational age alters susceptibility to TNFalpha, PAF and/or IL-1beta, and determine the role of the decidua in mediating the effects of these substances on myometrial contractile mechanisms. E. coli endotoxemia will be induced to determine E. coli endotoxemia alters contractile responses of pregnant uterus to TNFalpha, IL-1beta, oxytocin and PGF2alpha, and to determine if endotoxin is necessary to "prime" the gravid uterus and/or its decidua for expression of the myometrial effects of TNFalpha, and IL-1beta. These studies are designed to provide insight into cellular mechanisms responsible for the relationship of bacterial infection to premature labor. An understanding of these mechanisms could lead to the development of methods that would reduce premature births, as well as to a better comprehension of basic physiologic mechanisms that govern uterine function and parturition.

新生儿死亡和发病的最大原因是 早产 虽然导致早产的致病因素 分娩是未知的，最近的研究表明， 细菌感染可引起肿瘤坏死因子的释放 （TNF α）、白细胞介素1（IL-1 β）和血小板活化因子（PAF） 从蜕膜，然后预计会导致早产， 一些未知的机制。 我们提出了两个假设：TNF α， IL-1 β和PAF直接改变子宫肌层收缩功能， 内毒素血症改变子宫收缩特性。 收缩 TNF α、IL-1 β和PAF的作用将单独和联合检测。 与已知激动剂联合使用对TNF α、PAF和 IL-1 β被已知的受体拮抗剂改变，确定 胎龄改变对TNF α、PAF和/或IL-1 β的易感性， 确定蜕膜在介导这些影响中的作用 子宫肌层收缩机制的物质。 E.大肠杆菌内毒素血症将 诱导确定E.大肠杆菌内毒素血症改变了心肌的收缩反应 妊娠子宫对TNF α、IL-1 β、催产素和PGF 2 α的影响， 确定内毒素是否是“启动”妊娠子宫和/或其 蜕膜表达TNF α和IL-1 β的子宫肌层效应。 这些研究旨在提供对细胞机制的深入了解 负责细菌感染与早产的关系。 对这些机制的理解可以导致 减少早产的方法，以及更好的 了解控制子宫功能的基本生理机制 和分娩