Architectural Design of the Pelvic Floor Skeletal Muscles

盆底骨骼肌的结构设计

基本信息

批准号：
8491602
负责人：
Marianna Alperin
金额：
$ 7.75万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-25 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8491602
关键词：
Abdomen Affect Architecture Biochemical Biomechanics Birth Body Image Cadaver Childbirth Complex Connective Tissue Data Defecation Development Disease Early identification Etiology Event Extracellular Matrix Fecal Incontinence Female Fiber Functional disorder Generations Image Indium Individual Injury Intra-abdominal Intramuscular Knowledge Lead Life Link Measures Medicine Mental Depression Muscle Muscle function Myocardium Nature Organ Orthopedics Pathogenesis Pathologic Pelvic Floor Disorders Pelvic Floor Muscle Pelvic Pain Pelvic floor dysfunction Pelvic floor structure Pelvis Physiological Physiology Play Preventive Property Ptosis Quality of life Reporting Research Research Project Grants Risk Risk Factors Role Sexual Dysfunction Skeletal Muscle Social isolation Staging Striated Muscles Structure Study models Testing United States Urinary Incontinence Urination Ursidae Family Vagina Vaginal delivery procedure Viscera Woman abdominal pressure design human female human tissue improved interdisciplinary approach mechanical behavior muscular structure public health relevance therapy design

项目摘要

DESCRIPTION (provided by applicant): Pelvic floor disorders (PFD) include pelvic organ prolapse (POP), urinary incontinence, and fecal incontinence. Their impact on women is significant, causing pelvic pain, sexual dysfunction, social isolation, depression, and poor body image. PFD etiology is multifactorial and complex, with vaginal delivery identified as the leading risk factor for its development. The critical barrier that limits progress in identifying the precie cause of PFD is our lack of understanding of fundamental mechanisms that lead to pelvic floor dysfunction. Imaging and modeling studies have provided ample evidence that skeletal muscles are substantial contributors to pelvic floor support and are deleteriously affected by vaginal birt, but these reports have not causally linked vaginal birth, pelvic floor muscles' injury, and PFD in a mechanistic fashion. This significant knowledge gap makes it difficult to cultivate effective preventive measures and/or treatments for PFD. To define a potential mechanism that links pelvic floor striated muscle function and PFD, muscle architecture and the properties of its extracellular matrix (ECM) will be quantified. This will allow us to elucidate the structure-functin relationships in these muscles. In the field of orthopedics, significant advances in the treatment of muscular dysfunction became possible once precise muscles' structure, physiology and pathophysiology were established. An analogous leap forward is essential for progress to be realized in female pelvic medicine. In this proposal, we will define the architecture and intramuscular ECM of pelvic floor muscles from nulliparous and parous female human cadavers in order to understand specifics of these muscles' design and function that allow them to serve a complex dual role: provide support to the pelvic viscera and aid in continence, as well as facilitate urination, defecation, and parturition. We hypothesize that individual pelvic floor muscles' architecture and ECM are differentiated to allow for specialized roles in the pelvic floor Individual pelvic floor muscles are variably but permanently altered by vaginal deliveries, which compromises their function. These changes negatively impact biomechanical properties and contribute to the development of pelvic floor dysfunction later in life. The results of these studis will improve our understanding of events that cause pelvic floor muscles to switch from physiological to pathological remodeling and will have major implications in developing effective strategies for averting or delaying PFD. The interdisciplinary approach used in our research will have a significant impact on these vastly understudied conditions that negatively affect the lives of millions of women world-wide.

描述（由申请人提供）：骨盆底疾病（PFD）包括骨盆器官脱垂（POP），尿失禁和粪便失禁。她们对女性的影响很大，会导致骨盆疼痛，性功能障碍，社会隔离，抑郁和身体不良的形象。 PFD病因是多因素和复杂的，阴道分娩是其发育的主要危险因素。限制了识别PFD的前进原因的关键障碍是我们对导致骨盆底功能障碍的基本机制缺乏了解。成像和建模研究提供了充分的证据，表明骨骼肌是骨盆底支撑的重要贡献者，并受到阴道Birt的有害影响，但是这些报告并未因有因果关系而与阴道肌肉的损伤，PFD和PFD有因果关系。这种重要的知识差距使得为PFD培养有效的预防措施和/或治疗变得困难。为了定义将骨盆底肌功能和PFD连接起来的潜在机制，将量化肌肉结构及其细胞外基质（ECM）的特性。这将使我们能够阐明这些肌肉中的结构 - 函数关系。在骨科领域中，一旦建立了精确的肌肉结构，生理学和病理生理学，肌肉功能障碍的治疗就成为可能。向前的类似飞跃对于在雌性骨盆药物中实现的进步至关重要。在此提案中，我们将定义骨盆底肌肉的结构和肌内ECM，从无效的女性人类尸体中，以了解这些肌肉的设计和功能的细节，使它们能够发挥复杂的双重作用：为骨盆提供支持内脏和援助持续性，以及促进排尿，排便和分娩。我们假设单个骨盆底肌肉的结构和ECM有区别，以允许在骨盆底单个骨盆底肌肉中发挥专门的作用，但会因阴道递送而永久改变，从而损害其功能。这些变化对生物力学特性产生负面影响，并有助于盆腔底功能障碍的发展。这些研究的结果将提高我们对导致骨盆底肌肉从生理重塑转变为病理重塑的事件的理解，并将在制定有效的策略以避免或延迟PFD方面具有重要意义。我们研究中使用的跨学科方法将对这些经过深远影响的条件产生重大影响，这些条件会对全球数百万妇女的生活产生负面影响。