The Impact of Bowel Inflammation on Local Cystitis

间质性膀胱炎/痛性膀胱综合征(IC/PBS)被认为是一种局部表现 全身慢性炎症性疾病或状况。研究表明，多达50%的IC/PBS 患者有肠易激综合征(IBS)，而IBS患者也存在类似的IC/PBS高患病率 病人。动物研究表明，诱导结肠炎可以引起感觉 神经细胞在膀胱中释放神经肽，导致神经源性膀胱炎。然而， 尽管有这些观察，IBS并存对IC/PBS的影响仍不清楚。基于临床 和动物研究，我们假设局限性IC/PBS和IC/PBS合并IBS可能表现出类似的 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，这可能是 以分子和细胞水平的免疫学分析来区分。为了检验这一假设，我们将 进行以下三个具体目标：具体目标1)建立膀胱炎伴随模型 肠炎，并确定肠炎对局部膀胱炎的影响；具体目标2) 确定肠道炎症对膀胱对膀胱内治疗药物的反应的影响，并 开发有效的治疗膀胱炎合并肠炎的方法；具体目标3)建立炎症性 以及定位的IC/PBS和IC/PBS合并IBS的基因表达谱，并确定 伴发IBS对膀胱炎性/神经炎性物质表达的影响。我们将跨越我们的 新发展的Uro-OVA小鼠(一种新的膀胱炎模型)与Fabpl-OVA小鼠(AN 肠结肠炎模型)，以产生伴随肠炎的新的膀胱炎模型。然后我们将使用 Uro-OVA小鼠和Uro/Fabpl-OVA杂交小鼠(即局限性膀胱炎与伴肠性膀胱炎 炎症)来模拟人的IC/PBS和IC/PBS与IBS，以实现我们在动物模型中的研究目标。我们 还将分析人类生物样本，以建立炎症和基因表达谱 伴有和不伴有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 在局限性IC/PBS和伴有肠炎的IC/PBS之间，提供了一个有用的全身性IC/PBS模型， 并有助于IC/PBS患者新诊断和治疗的未来发展

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