Iatrogenic Injury Recapitulated: Electroexcision Technique for Urethral Stricture Modeling in Rats

Summary

In this study, we present a novel, efficient, and stable rat model of urethral stricture created through electroexcision of the rat urethra, which effectively simulates iatrogenic injury observed in clinical settings.

Abstract

Urethral stricture (US) is a common clinical condition in urology, characterized by high prevalence and morbidity across all ages. Current treatments for US, such as urethral dilatation and internal urethrotomy, fail to fully resolve the condition and are associated with high rates of recurrence and complications.

Additionally, the pathogenesis of US is not well understood. To explore the pathogenesis of US and develop new therapeutic strategies, it is crucial to establish a standardized rat model that accurately reflects the clinical manifestations. This study outlines a straightforward and repeatable method for inducing US in rats using a high-frequency electric knife. The method involves making a longitudinal incision with the electric knife set to a unipolar mixed cutting mode at 4 W, which inflicts significant urethral damage. Histopathological analysis shows thickening of the urothelium, inflammatory infiltration, and disorganized collagen fibers. This model effectively replicates iatrogenic injury through electroexcision in the rat urethra. In summary, this study successfully establishes a new, efficient, and stable rat model of US that closely mimics the clinical scenario, providing a valuable tool for further research into the mechanisms and novel treatments for US.

Introduction

Urethral stricture (US) is among the oldest urologic conditions and continues to be widely prevalent. Recent data suggest that there are between 229 and 627 cases of US per 100,000 males¹. Those suffering from US experience a range of symptoms including lower urinary tract symptoms², pain³, and sexual dysfunction⁴. Several medical treatments are available, such as urethrotomy, urethroplasty, and dilation⁵. However, these treatments are often complicated by issues such as bleeding, infection, and incontinence, contributing to the disease burden and ex....

Protocol

In this investigation, twenty 6-month-old male Sprague-Dawley rats, each weighing 400-500 g, were employed. All animal procedures were conducted in accordance with the guidelines of the Institutional Animal Care and Use Committee at the Fifth Affiliated Hospital of Sun Yat-Sen University (Approval number: 00349). The animals were housed in a facility with controlled temperature and lighting conditions. A fundamental characteristic of urethral stricture is the development of scarring within the urethra. Based on the estab.......

Discussion

US pose a significant healthcare burden with a substantial economic impact, adversely affecting both psychological and physical well-being²⁰. There is still a need for a treatment that not only completely cures US but also effectively prevents its recurrence.

In this study, we utilized a rat model to develop a straightforward and reproducible method for mimicking urethral injury in patients, which was followed by transurethral surgery-induced urethral injury. Rats are f.......

Materials

Name	Company	Catalog Number	Comments
absorbable sutures (6-0)	KERONG COMPANY	KR2230814
Animal operating pad	Provided by Guangdong Provincial Key Laboratory of Biomedical Imaging	NA
CaseViewer 2.4	3DHISTECH Ltd.
Carprofen	Sigma-Aldrich	MFCD00079028
CoraLite488-conjugated Goat Anti-Rabbit IgG(H+L)	Proteintech	SA00013-2
H&E Stain Kit	Abcam	ab150669
high-frequency electrosurgical unit	Beijing Taktvoll Technology Company	ES-100v
Masson staining kit	Merck	HT15
needle-holding pliers	RWD Life Science	S15001-11
Paraffin oil	NA	NA
smooth forceps	RWD Life Science	F13019-12
Sodium pentobarbital	Guangdong Provincial Key Laboratory of Biomedical Imaging	NA
Sprague–Dawley rat	Guangdong Medical Laboratory Animal Center	GDMLAC-035
suture scissors	RWD Life Science	S15001-11
Teflon coated catheter (0.6 mm x 1 mm)	DGZF new materials company	NA
TGF Beta 1 Polyclonal antibody	Proteintech	21898-1-AP
Tissue scissors	RWD Life Science	S13029-14