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：
8689130
负责人：
Marianna Alperin
金额：
$ 7.53万
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 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8689130
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）：盆底疾病（PFD）包括盆腔器官脱垂（POP）、尿失禁和大便失禁。它们对女性的影响是巨大的，导致骨盆疼痛、性功能障碍、社会孤立、抑郁和不良的身体形象。 PFD 病因是多因素且复杂的，阴道分娩被认为是其发生的主要危险因素。限制 PFD 确切原因进展的关键障碍是我们对导致盆底功能障碍的基本机制缺乏了解。影像学和建模研究提供了充足的证据，表明骨骼肌对盆底支撑有重要贡献，并受到阴道分娩的有害影响，但这些报告并未以机械方式将阴道分娩、盆底肌肉损伤和 PFD 联系起来。这种巨大的知识差距使得制定有效的 PFD 预防措施和/或治疗方法变得困难。为了定义连接盆底横纹肌功能和 PFD 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的结构-功能关系。在骨科领域，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可能取得重大进展。类似的飞跃对于女性盆腔医学的进步至关重要。在本提案中，我们将定义来自未产和已产女性尸体的盆底肌肉的结构和肌内 ECM，以便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帮助失禁，以及促进排尿、排便和分娩。我们假设个体盆底肌肉的结构和 ECM 是不同的，以允许在盆底中发挥专门的作用。个体盆底肌肉会因阴道分娩而发生不同但永久性的改变，从而损害其功能。这些变化会对生物力学特性产生负面影响，并导致晚年盆底功能障碍的发展。这些研究的结果将提高我们对导致盆底肌肉从生理重塑转变为病理重塑的事件的理解，并将对制定避免或延迟 PFD 的有效策略产生重大影响。我们研究中使用的跨学科方法将对这些严重不足的研究产生重大影响，这些条件对全世界数百万女性的生活产生了负面影响。