The Role of Altered Permeability in Bladder Diseases

渗透性改变在膀胱疾病中的作用

• 批准号: 8549231
• 负责人: ROBERT Evan HURST
• 金额: $ 30万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-29 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8549231
• 关键词: Acute; Address; Adult; Affect; Age; Aging; Animal Model; Animals; Basic Science; Benign; Biological Markers; Birth; Bladder; Bladder Diseases; Bladder Dysfunction; Bladder Exstrophy; Cells; Child; Chondroitin Sulfates; Chronic; Clinical; Clinical Research; Comorbidity; Data; Distress; Feasibility Studies; Fibrosis; Healed; Health; Health Care Costs; Healthcare Systems; Human; Individual; Infant; Inflammation; Interstitial Cystitis; Intestines; Investigation; Knowledge; Longevity; Maps; Measures; Methods; Modeling; Molecular; Muscle; Natural regeneration; Neurosciences; Organ; Overactive Bladder; Pathology; Patients; Permeability; Physiological; Plague; Plant Roots; Population; Positioning Attribute; Prevalence; Proteins; Proteome; Quality of life; Race; Rattus; Recovery; Research Personnel; Role; System; Testing; Trauma; Urine; Urologic Diseases; Urology; Urothelium; Vascularization; afferent nerve; age related; aged; cost; design; healing; hyaluronate; improved; interdisciplinary approach; intravesical; macrophage; mast cell; nanoparticle; patient population; programs; protein expression; response

DESCRIPTION (provided by applicant): We hypothesize that there is a unifying mechanism associated with acute or chronic factors that damage the impermeability barrier that normally protects the bladder. Thus, we propose that increased permeability of the bladder is a root cause of many benign bladder diseases. (1) In bladder regeneration, the race between healing and fibrosis is tipped in favor of fibrosis by permeability of the nascent organ to urine, and we will investigate with animal models how decreasing permeability of the regenerating bladder facilitates healing. (2) In IC/PBS, depolarization of sensory nerves and structural changes induced by leakiness underlie that pathology. Comorbidity studies suggest that a reciprocal relationship exists between bowel and bladder such that changes in one induces permeability changes in the other, and animal studies of this reciprocity will reveal mechanisms relevant to clinical populations. Increased permeability may be a factor in OAB as well. We, therefore, plan a clinical study to determine the role of increased permeability in IC/PBS and CPP and LUTS as a function of aging.

描述（由申请人提供）：我们假设存在与急性或慢性因素相关的统一机制，这些因素会损害通常保护膀胱的不渗透性屏障。因此，我们认为膀胱通透性增加是许多良性膀胱疾病的根本原因。(1)在膀胱再生中，愈合和纤维化之间的竞赛通过新生器官对尿液的渗透性而倾向于纤维化，我们将用动物模型研究再生膀胱的渗透性如何降低以促进愈合。(2)在IC/PBS中，感觉神经的去极化和由泄漏引起的结构变化是病理学的基础。同期研究表明，肠道和膀胱之间存在相互关系，其中一个的变化会引起另一个的渗透性变化，这种相互关系的动物研究将揭示与临床人群相关的机制。增加的渗透性也可能是OAB的一个因素。因此，我们计划进行一项临床研究，以确定IC/PBS和CPP和LUTS中渗透性增加的作用作为老化的函数。