An Immature Murine Model of Reversible Unilateral Ureteral Obstruction

Summary

The present protocol describes a step-by-step, reproducible model of unilateral ureteral obstruction.

Abstract

Unilateral ureteral obstruction (UUO) is a common cause of chronic kidney disease (CKD), leading to the progression of renal interstitial fibrosis and ultimately resulting in irreversible kidney damage. The alleviation of UUO is crucial. Several animal models of reversible unilateral ureteral obstruction (RUUO) have been established in the literature, enabling the observation of structural changes and functional damage while also simulating physiological and pathophysiological changes following the relief of ureteral obstruction. In this study, a reversible obstruction model was established in the unilateral murine ureter using a silicone tube. Significant renal damage was observed prior to obstruction relief, with partial recovery noted afterward. Unlike UUO, this model prevents progressive hydronephrosis, leading to distinct pathological outcomes. This simple surgical procedure demonstrates a high success rate and holds promise as a classical model for investigating reversible obstructive nephropathy and potential treatments for renal interstitial fibrosis. Furthermore, it provides a practical platform for studying the mechanisms of recovery from obstructive nephropathy, renal cell regeneration, and tissue remodeling.

Introduction

Urethral obstruction significantly contributes to renal interstitial fibrosis and chronic kidney disease (CKD), potentially leading to irreversible structural damage and functional impairments in the kidney¹. While unilateral ureteral obstruction (UUO) is widely used to study kidney injury and CKD, it does not accurately replicate the spontaneous recovery mechanisms that occur after the removal of an obstruction. The UUO model involves ligating the left ureter with sutures, resulting in permanent obstruction, ureteral dilation, hydronephrosis, compression of the renal parenchyma, and cortical thinning. Histological examination typically reveals

Protocol

This animal study adhered to the guidelines of the Declaration of Helsinki and was approved by the Research Ethics Committee of the Children's Hospital of Chongqing Medical University. A total of 27 male Sprague Dawley (SD) rats were commercially obtained and housed in the Laboratory Animal Center of the Children's Hospital of Chongqing Medical University (SPF, license number: SYXK (Chongqing) 2007-0016). The rats were maintained under controlled temperature conditions with a 12-h light/dark cycle and had ad libitum access to food and water.

The protocol was conducted on male SD rats aged 6-8 weeks and is applicable to rats

Results

The effects of UUO and its subsequent release (RUUO) on body weight, kidney weight, kidney volume, and serum creatinine (Scr) levels were evaluated, as summarized in Table 1. Data are presented as mean ± standard deviation (SD), with n = 5 per group.

At 6 weeks, the native group exhibited a mean body weight of 234 g ± 16 g, kidney weight of 0.9107 g ± 0.0475 g, and kidney volume of 0.8962 cm³ ± 0.0502 cm³. By 8 weeks, the control group showed sign...

Discussion

This model employs a silicone tube to encircle the ureter, providing structural support, followed by ligation with a silk thread to induce complete ureteral obstruction through compression. After seven days, the ligation and silicone tube are removed to facilitate kidney decompression and the restoration of urinary tract integrity and functionality.

Silicone tubing, manufactured from silicone elastomers, offers excellent flexibility, biocompatibility, chemical resistance, and thermal stability...

Materials

Name	Company	Catalog Number	Comments
Forceps	Shanghai Medical Devices Co.,Ltd	20220032
Gauze	Sichuan Kelun Co., Ltd	20172140152
Hematoxylin and Eosin Stain Kit	Solarbio	G1120
Insulin needles	KDL Medical Devices	20193140938
Masson’s Trichrome Stain Kit	Solarbio	G1340
Medical Cotton balls	Sichuan Kelun Co., Ltd	20170037
Medical Cotton sticks	Sichuan Kelun Co., Ltd	20172140026
Methylene blue	Tianjin Dengfeng Chemical Reagent Factory	14038-43-8
Microscopic forceps	Suqian Shifeng Medical Devices Co., Ltd	S50985
Needle holders	Suqian Shifeng Medical Devices Co., Ltd	S7005
Povidone-iodine Solution	Sichuan Kelun Co., Ltd	514001
Saline	Sichuan Kelun Co., Ltd	20220004
SD Rats	SPF(Beijing)Biotechnology Co.,Ltd	D025
Silicone tubing	Taizhou Chunshi New Materials Co., Ltd	CS356
Silk suture	Qiangsheng Medical Devices Co.,Ltd	SA84G
Surgical blade	Huanan Yunyue Medical Devices Co.,Ltd	CE0434
Surgical scissors	Shanghai Medical Devices Co.,Ltd	J21130
Syringe	Tongmai medical devices	20183140304
Tissue Forceps	Jiangxi Yuyuan Medical Equipment Co., Ltd	J36030