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FACTORS RESPONSIBLE FOR THE CONTROL OF HUMAN LABOR

控制人类劳动的因素

基本信息

批准号：
6654451
负责人：
ROGER C. YOUNG
金额：
$ 23.19万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-01-01 至 2004-12-31
项目状态：
已结题

项目摘要

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.

这项提议将阐明人类怀孕的子宫如何协调子宫肌层细胞功能与子宫收缩功能的关系。获得的知识从这项工作中将定义负责协调的因素，产程的启动、维持。这些问题是密切相关的与早产、过期妊娠和功能障碍有关分娩，与早产、胎儿窘迫直接相关，以及剖腹产率。加深了对子宫收缩能力的理解将潜在地允许治疗分娩异常指向潜在的生理异常。我们有最近开发了一种假设的初始形式，该假说指定了子宫细胞在人类分娩过程中进行交流。这一型号包含了具有局部机制的全球(整个子宫)。这个这种模式的本质是器官层面的交流是通过行动进行的潜在的传播，但负责启动的信号每个细胞的收缩都是由细胞间钙波进行的。这一假说因此被称为动作电位-钙波。假说(AP波假说)。这项研究的目的是检验基础和配方 AP波假说，并在缺点出现时对其进行修改确认身份。这一假说的演变形式有望使临床医生追踪特定的分娩临床参数(如子宫收缩的强度和频率)回到细胞机制。结果，特定的劳动异常(间隔不良宫缩，对催产素的异常反应，基线升高压力和许多其他因素)将能够与特定的细胞功能。这一知识将为选择一种特殊治疗方法的科学依据特别是产程异常。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) 了解钙代谢和信号传递的目标组织。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，即将为基础的教育、研究和应用提供基础将科学知识转化为临床医学知识。