We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder.
Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis.
In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups.
Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.
International neurourology journal. 2017 Sep 12 [Epub]
Phil Hyun Song, So Young Chun, Jae-Wook Chung, Yeon Yong Kim, Hyo Jung Lee, Jun Nyung Lee, Yun-Sok Ha, Eun Sang Yoo, Tae Gyun Kwon, Jeongshik Kim, Dae Hwan Kim, Bum Soo Kim
Department of Urology, Yeungnam University College of Medicine, Daegu, Korea., BioMedical Research Institute, Kyungpook National University Hospital, Daegu, Korea., Department of Urology, Kyungpook National University School of Medicine, Daegu, Korea., Department of Pathology, Central Hospital, Ulsan, Korea., Department of Laboratory Animal Research Support Team, Yeungnam University Hospital, Daegu, Korea.