Int Neurourol J.  2017 Sep;21(3):163-170. 10.5213/inj.1734898.449.

Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research Into Interstitial Cystitis

• Song PH
• Chun SY
• Chung JW
• Kim YY
• Lee HJ
• Lee JN
• Ha YS
• Yoo ES
• Kwon TG
• Kim J
• Kim DH
• Kim BS

• KMID: 2396151
• DOI: http://doi.org/10.5213/inj.1734898.449

Abstract

PURPOSE
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.

Keyword

Cystitis, Interstitial; Models, Animal; Rats; Immunization

MeSH Terms

Acetic Acid
Animals
Animals*
Chemokine CCL2
Cyclophosphamide
Cystitis, Interstitial*
Female
Fibrosis
Gene Expression
Humans
Hydrochloric Acid
Hyperplasia
Immunization
Injections, Intraperitoneal
Injections, Subcutaneous
Interleukin-6
Mast Cells
Models, Animal*
Peroxidase
Rats*
Rats, Sprague-Dawley
Toll-Like Receptors
Urinary Bladder
Uroplakin II
Acetic Acid
Chemokine CCL2
Cyclophosphamide
Hydrochloric Acid
Interleukin-6
Peroxidase
Toll-Like Receptors
Uroplakin II