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Sources of Funding: This work was supported by Basic Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning under Grant (NRF-2015R1C1A1A01053509).

Introduction

Interstitial cystitis (IC) is a chronic bladder disorder characterized by urinary frequency, urgency and pelvic pain in the absence of bacterial infection or identifiable pathology. To date, there is no reliably effective therapy for IC, and no generally accepted animal model to test novel therapies was established. We therefore analyzed and compared the characterization of five different promising rat models to establish the best interstitial cystitis animal model.

Methods

Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M HCl (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK). Phosphate-buffered saline was transurethrally infused for the control group (PBS). After generating IC models, conscious cystometry was performed at day 3, 7, and 14. All rats were euthanized at day 14 and the bladders were removed for histological, immunohistochemical analysis and real-time quantitative polymerase chain reaction (PCR).

Results

In cystometric analysis, all experimental groups, including HCl, AA, CYP, LPS, and UPK, showed significantly decreased intercontraction intervals compared with control group at day 3, but only LPS and UPK group exhibited urinary frequency compared to control and other experimental groups at day 14. Histological analysis revealed that markedly increased infiltration of Toluidine blue-stained mast cells and significantly increased tissue fibrosis in LPS and UPK groups compared to the other groups. PCR analysis showed significantly elevated expression of interleukin-1b, -6, -17a, myeloperoxidase, monocyte chemotactic protein-1, toll-like receptors 2 and 4 in UPK group compared with the other groups.

Conclusions

Rat models generated by infusion of HCl, AA, CYP, LPS and UPK displayed urinary frequency up to 7 days and appropriate histologic changes similar to human interstitial cystitis. However, our study demonstrated that injection of UPK can be the best method to establish the interstitial cystitis rat model, considering longer continuation of bladder overactivity and higher expression of inflammatory factors.

Funding

This work was supported by Basic Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning under Grant (NRF-2015R1C1A1A01053509).