The Impact of Bowel Inflammation on Local Cystitis

肠道炎症对局部膀胱炎的影响

• 批准号: 7571854
• 负责人: YI LUO
• 金额: $ 11.5万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7571854
• 关键词: Afferent Neurons; Animal Model; Animals; Back; Basic Science; Behavior; Biological; Biological Markers; Bladder; CD4 Positive T Lymphocytes; CD8B1 gene; Calmette-Guerin Bacillus; Chronic; Clinical; Condition; Cromolyn Sodium; Crossbreeding; Cystitis; Development; Diagnosis; Disease; Enterocolitis; Exhibits; Functional disorder; Future; Gene Expression; Goals; High Prevalence; Histopathology; Human; Immunosuppressive Agents; Inflammation; Inflammatory; Interstitial Cystitis; Intervention; Intestines; Irritable Bowel Syndrome; Light; Localized; Mast Cell Stabilizer; Messenger RNA; Modeling; Molecular; Molecular Profiling; Mus; Neurogenic Bladder; Neurogenic Inflammation; Neurons; Neuropeptides; Oral; Pain; Pathogenesis; Patients; Peptides; Proteins; RDP58; Research; Serum; Specimen; Symptoms; T-Lymphocyte; Testing; Therapeutic Agents; Tissues; Transgenic Mice; Urination; Urine; base; chemokine; clinically relevant; cytokine; immunopathology; improved; intraperitoneal; intravesical; mast cell; novel; painful bladder syndrome; response; urologic

Interstitial cystitis/painful bladder syndrome (IC/PBS) has been suggested to be a local manifestation of a systemic chronic inflammatory disease or condition. Studies have shown that as many as 50% of IC/PBS patients have irritable bowel syndrome (IBS) whereas a similar high prevalence of IC/PBS presents in IBS patients. Animal studies have demonstrated that induction of colonic inflammation could cause sensory neurons in the bladder to release neuropeptides, leading to neurogenic bladder inflammation. However, despite these observations, the impact of co-presence of IBS on IC/PBS remains unclear. Based on clinical and animal studies, we hypothesize that both localized IC/PBS and IC/PBS with IBS could exhibit similar urological dysfunctions and pain symptoms; however, they are distinctive in pathophysiology, which can be distinguished by immunological analysis at the molecular and cellular levels. To test this hypothesis, we will conduct the following three specific aims: Specific Aim 1) To establish a cystitis model with concomitant bowel inflammation, and determine the impact of bowel inflammation on local cystitis; Specific Aim 2) To determine the impact of bowel inflammation on bladder response to intravesical therapeutic agents, and to develop effective therapy for cystitis with bowel inflammation; Specific Aim 3) To establish the inflammatory and gene expression profiles for localized IC/PBS and IC/PBS with IBS, and determine the impact of concomitant IBS on bladder expression of inflammatory/neuroinflammatory substances. We will cross our newly developed URO-OVA mice (a novel bladder inflammation model) with Fabpl-OVA mice (an enterocolitis model) to generate a new cystitis model with concomitant bowel inflammation. We will then use both URO-OVA mice and the crossed URO/Fabpl-OVA mice (i.e. localized cystitis vs. cystitis with bowel inflammation) to mimic human IC/PBS and IC/PBS with IBS to fulfill our study goals in animal models. We will also analyze human biological specimens to establish inflammatory and gene expression profiles for IC/PBS both with and without IBS. Key factors will be identified and new biomarkers will be explored. Successful completion of this study will improve our understanding of the differential immunopathology between localized IC/PBS and IC/PBS with bowel inflammation, provide a useful systemic IC/PBS model, and aid future development of new diagnosis and treatment for IC/PBS patients

间质性膀胱炎/膀胱疼痛综合征（IC/PBS）被认为是一种局部表现， 全身性慢性炎性疾病或病症。研究表明，多达50%的IC/PBS 患者患有肠易激综合征（IBS），而在IBS患者中IC/PBS的患病率相似 患者动物研究表明，诱导结肠炎症可引起感觉神经元损伤。 膀胱中的神经元释放神经肽，导致神经源性膀胱炎症。然而，在这方面， 尽管有这些观察结果，IBS的共存对IC/PBS的影响仍然不清楚。基于临床 和动物研究，我们假设局部IC/PBS和IC/PBS与IBS可以表现出类似的 泌尿系统功能障碍和疼痛症状;然而，它们在病理生理学上是独特的， 通过在分子和细胞水平上的免疫学分析来区分。为了验证这个假设，我们将 具体目的1）建立膀胱炎模型， 肠道炎症，并确定肠道炎症对局部膀胱炎的影响;具体目的2） 确定肠道炎症对膀胱对膀胱内治疗剂的反应的影响， 为膀胱炎伴肠道炎症开发有效的治疗方法;具体目标3）建立炎症 和局部IC/PBS和IC/PBS与IBS的基因表达谱，并确定 伴随IBS对膀胱表达的炎症/神经炎症物质的影响。我们将跨越我们的 新开发的URO-OVA小鼠（一种新的膀胱炎症模型）与Fabpl-OVA小鼠（一种新的膀胱炎模型） 小肠结肠炎模型）以产生伴随肠道炎症的新膀胱炎模型。然后我们将使用 URO-OVA小鼠和杂交的URO/Fabp 1-OVA小鼠（即局部膀胱炎对肠梗阻性膀胱炎 炎症）来模拟人IC/PBS和具有IBS的IC/PBS，以实现我们在动物模型中的研究目标。我们 还将分析人类生物标本，以建立炎症和基因表达谱， 有和无IBS的IC/PBS。将确定关键因素，并探索新的生物标志物。 这项研究的成功完成将提高我们对差异免疫病理学的理解， 在局部IC/PBS和IC/PBS与肠道炎症之间，提供了有用的全身IC/PBS模型， 并有助于IC/PBS患者的新诊断和治疗的未来发展