FACTORS RESPONSIBLE FOR THE CONTROL OF HUMAN LABOR

控制人类劳动的因素

• 批准号: 2758503
• 负责人: ROGER C. YOUNG
• 金额: $ 21.97万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2758503
• 关键词: action potentials; biological signal transduction; birth; calcium flux; calcium ion; calcium metabolism; cell cell interaction; clinical research; confocal scanning microscopy; electrodes; electrophysiology; fluorescence microscopy; gap junctions; human pregnant subject; labor complications; membrane channels; muscle cells; muscle contraction; myofibrils; myometrium; pregnancy; prostaglandins; uterus; voltage /patch clamp

This proposal will elucidate how the human pregnant uterus coordinates myometrial cell function with uterine contractility. Knowledge gained from this work will define the factors responsible for the coordination, initiation, and maintenance of labor. These issues are intimately associated with preterm labor, postdates pregnancy, and dysfunctional labor, which correlate directly with prematurity, fetal distress, and cesarean section rates. Improved understanding of uterine contractility will potentially allow treatments of an abnormality of labor to be directed towards the underlying physiological abnormality. We have recently developed the initial form of a hypothesis that specifies how the uterine cells communicate in human labor. This model incorporates global (throughout the entire uterus) with local mechanisms. The essence of this model is that organ-level communication is by action potential propagation, but the signal responsible for initiating contraction of each cell is carried by intercellular calcium waves. This hypothesis is therefore called the action potential - calcium wave hypothesis (AP-wave hypothesis). The purpose of this research is to test the foundation and formulation of the AP-wave hypothesis and to modify it when shortcomings are identified. The evolving form of this hypothesis will hopefully allow clinicians to trace specific clinical parameters of labor (such as strength and frequency of uterine contractions) back to cellular mechanisms. As a result, specific abnormalities of labor (poor spacing of contractions, abnormal response to oxytocin, elevated baseline pressure, and many others) would then be able to be correlated with specific cellular functions. This knowledge would provide the scientific basis for the selection of a particular therapy for a particular abnormality of labor. We propose a combination of techniques (structural studies of tissue, confocal microscopy, electrophysiology and calcium dye imaging) with a goal of understanding calcium metabolism and signal transmission through tissue. At the conclusion of this project we will have an improved understanding of the functional unit of the human pregnant uterus, which will provide the basis for education, research, and application of basic science knowledge to clinical medicine.

这个建议将阐明人类怀孕子宫如何协调 子宫肌细胞功能与子宫收缩力。获得的知识 从这项工作中将确定负责协调的因素， 启动和维持劳动力。 这些问题密切相关 与早产、过期妊娠和功能障碍有关 分娩，与早产、胎儿窘迫和 剖腹产率 提高对子宫收缩力的认识 将有可能使分娩异常的治疗 指向潜在的生理异常 我们有 最近开发了一个假设的初始形式，该假设详细说明了 子宫细胞在人类分娩时进行交流。 该模型包含 全局（遍及整个子宫），具有局部机制。 的 这个模型的本质是器官层面的交流是通过动作进行的 潜在的传播，但负责发起的信号 每个细胞的收缩由细胞间钙波携带。 这一假说因此被称为动作电位-钙波 AP波假说（AP-wave hypothesis） 本研究的目的是检验基础和配方 的AP波假说，并修改它时，缺点是 鉴定 这种假设的发展形式有望让 临床医生追踪分娩的特定临床参数（例如， 子宫收缩的强度和频率）回到细胞 机制等 因此，分娩的特定异常（间隔不良 宫缩，催产素反应异常，基线升高 压力，以及许多其他），然后将能够与 特定的细胞功能。 这些知识将提供 选择特定疗法的科学依据 特别是异常的劳动。 我们提出了一种技术组合（组织结构研究， 共聚焦显微镜、电生理学和钙染料成像）， 目的是了解钙代谢和信号传递， 组织. 在这个项目结束时，我们将有一个改进的 了解人类妊娠子宫的功能单位， 将为基础教育、研究和应用提供基础。 科学知识到临床医学。