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间质性膀胱炎/膀胱疼痛综合征的动物模型。

Animal models of interstitial cystitis/bladder pain syndrome.

作者信息

Tay Cindy, Grundy Luke

机构信息

Neurourology Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute, Flinders University, Adelaide, SA, Australia.

出版信息

Front Physiol. 2023 Sep 4;14:1232017. doi: 10.3389/fphys.2023.1232017. eCollection 2023.

Abstract

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic disorder characterized by pelvic and/or bladder pain, along with lower urinary tract symptoms that have a significant impact on an individual's quality of life. The diverse range of symptoms and underlying causes in IC/BPS patients pose a significant challenge for effective disease management and the development of new and effective treatments. To facilitate the development of innovative therapies for IC/BPS, numerous preclinical animal models have been developed, each focusing on distinct pathophysiological components such as localized urothelial permeability or inflammation, psychological stress, autoimmunity, and central sensitization. However, since the precise etiopathophysiology of IC/BPS remains undefined, these animal models have primarily aimed to replicate the key clinical symptoms of bladder hypersensitivity and pain to enhance the translatability of potential therapeutics. Several animal models have now been characterized to mimic the major symptoms of IC/BPS, and significant progress has been made in refining these models to induce chronic symptomatology that more closely resembles the IC/BPS phenotype. Nevertheless, it's important to note that no single model can fully replicate all aspects of the human disease. When selecting an appropriate model for preclinical therapeutic evaluation, consideration must be given to the specific pathology believed to underlie the development of IC/BPS symptoms in a particular patient group, as well as the type and severity of the model, its duration, and the proposed intervention's mechanism of action. Therefore, it is likely that different models will continue to be necessary for preclinical drug development, depending on the unique etiology of IC/BPS being investigated.

摘要

间质性膀胱炎/膀胱疼痛综合征(IC/BPS)是一种慢性疾病,其特征为盆腔和/或膀胱疼痛,以及下尿路症状,这些症状对个人生活质量有重大影响。IC/BPS患者症状多样且病因各异,这给有效管理该疾病以及开发新的有效治疗方法带来了重大挑战。为了促进IC/BPS创新疗法的开发,已建立了许多临床前动物模型,每个模型都聚焦于不同的病理生理成分,如局部尿路上皮通透性或炎症、心理压力、自身免疫和中枢敏化。然而,由于IC/BPS的确切病因病理生理学仍不明确,这些动物模型主要旨在复制膀胱超敏反应和疼痛的关键临床症状,以提高潜在治疗方法的可转化性。目前已有几种动物模型被描述为可模拟IC/BPS的主要症状,并且在优化这些模型以诱导更类似于IC/BPS表型的慢性症状方面取得了重大进展。然而,需要注意的是,没有一个单一模型能够完全复制人类疾病的所有方面。在选择用于临床前治疗评估的合适模型时,必须考虑特定患者群体中被认为是IC/BPS症状发展基础的具体病理,以及模型的类型和严重程度、其持续时间以及拟议干预措施的作用机制。因此,根据所研究的IC/BPS的独特病因,不同的模型可能仍将是临床前药物开发所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/10507411/c4c38cea64e5/fphys-14-1232017-g001.jpg

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