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Medicine
评估长期单侧输尿管梗阻逆转后长期结构和功能结局的小鼠模型
评估长期单侧输尿管梗阻逆转后长期结构和功能结局的小鼠模型
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Medicine
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JoVE Journal Medicine
A Mouse Model to Evaluate the Long-Term Structural and Functional Outcomes after the Reversal of Prolonged Unilateral Ureteric Obstruction

评估长期单侧输尿管梗阻逆转后长期结构和功能结局的小鼠模型

Full Text
598 Views
05:34 min
July 18, 2025

DOI: 10.3791/68492-v

Rachel D. Delagado1, Mark P. de Caestecker1

1Division of Nephrology, Department of Medicine,Vanderbilt University Medical Center

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Please note that some of the translations on this page are AI generated. Click here for the English version.

Overview

This study presents a standardized protocol for performing reversible unilateral ureteric obstruction in mice, facilitating the analysis of long-term outcomes following the reversal of urinary obstruction.

Key Study Components

Area of Science

  • Nephrology
  • Animal Models
  • Kidney Injury Research

Background

  • Investigating long-term outcomes after kidney injury is crucial for developing effective therapies.
  • Current methods often require complex surgical skills or multiple surgeries.
  • This model allows for functional evaluation without extensive surgical expertise.
  • Unilateral obstruction provides a unique opportunity to assess recovery without split renal function tests.

Purpose of Study

  • To develop a reliable mouse model for studying long-term outcomes after urinary obstruction reversal.
  • To simplify the surgical procedure for broader accessibility in research labs.
  • To evaluate functional and structural kidney recovery post-obstruction.

Methods Used

  • Preparation of the surgical site and anesthetization of the mouse.
  • Creation of a longitudinal incision to access the kidney and ureter.
  • Placement of a vascular clamp to induce obstruction.
  • Removal of the clamp and assessment of kidney function and structure over time.

Main Results

  • Functional studies demonstrated significant differences in kidney function between obstructed and nephrectomized mice.
  • Urinary osmolarity was markedly lower in nephrectomy control mice.
  • Long-term outcomes were effectively monitored using this model.
  • The protocol allows for consistent and reproducible results across experiments.

Conclusions

  • This model provides a valuable tool for studying kidney recovery post-obstruction.
  • It simplifies the surgical process, making it accessible to more research laboratories.
  • The findings contribute to understanding the mechanisms of kidney injury and recovery.

Frequently Asked Questions

What is reversible unilateral ureteric obstruction?
It is a surgical procedure that temporarily obstructs one ureter to study kidney function and recovery.
Why is this model important?
It allows researchers to evaluate long-term kidney recovery without complex surgical techniques.
How does this model compare to other methods?
It is less invasive and requires fewer surgical skills than traditional methods.
What outcomes can be measured?
Functional outcomes such as blood urea nitrogen and urinary osmolarity can be assessed.
How long after the procedure are measurements taken?
Measurements are typically taken 84 days after the reversible obstruction.
Can this model be used in other research areas?
Yes, it can be adapted for various studies related to kidney injury and recovery.

本文提供了详细说明,使研究人员能够使用标准化模型对小鼠进行可逆的单侧输尿管梗阻,该模型允许分析长期输尿管梗阻逆转后的长期结构和功能结果。

我的实验室致力于改善肾损伤后长期结果的机制和治疗方法,该方案的具体重点是开发一种工具来研究尿路梗阻逆转后的长期结果。我们开发了单侧可逆性输尿管梗阻的小鼠模型,这使我们能够评估逆转肾脏尿路梗阻的长期功能和结构结果。其他方法需要多次手术或显微外科专业知识,而大多数实验室无法获得这些专业知识。此外,由于这是单侧梗阻,大多数其他方法不允许在不进行分体肾功能测试的情况下对恢复进行功能评估。实际上只有两个。第一个是每次实验中将血管夹一致地放置在输尿管近端的同一位置,第二个是在几天后移除血管夹,而不会对输尿管或肾脏造成损害。

[雷切尔]首先,用防腐剂准备麻醉小鼠的手术侧。使用剪刀和镊子沿中线穿过皮肤和皮下层做一个 1.5 厘米的纵向背侧切口。在肾脏上方的左侧肌肉和筋膜上做一个小切口。然后用一把镊子,将左肾外化。使用钝镊子。仔细解剖下极的脂肪和输尿管附近的一些结缔组织。找到输尿管区域。然后将输尿管及其结缔组织与肾蒂分开,以避免将肾静脉和动脉夹入夹子。使用夹钳应用器打开血管夹并将其放置在输尿管肾盂的正下方。使用夹子上的标记以确保在所有小鼠身上施加均匀的压力。现在使用浸有盐水的无菌棉签将带有夹子的肾脏轻轻推回腹膜后空间。然后使用可吸收缝合线缝合肌肉层。使用蒙皮夹关闭蒙皮图层。要移除输尿管夹,请取下伤口夹,然后清洁手术区域,不要使用原始切口重新塑造以接触夹子。重新打开肌肉层并暴露腹膜后空间。使用镊子小心地将夹子定位在腹膜后空间中,不要将肾脏外部化。使用夹子应用器,轻轻打开夹子,同时使用镊子将周围组织拉开以安全地将其取出。现在将肾脏外部化以检查肾盂是否有阻塞。肾盂肿胀证实肾积水。使用浸有盐水的无菌棉签将肾脏推回腹膜后空间,并按照图示缝合切口。要进行对侧肾切除术,请使用原始皮肤切口重新打开背侧部位。在大小上,右侧肌肉和肾脏上方的筋膜。然后使用镊子将右肾外部化。用光滑、弯曲的镊子握住右肾,并解剖上下两极,使其远离周围组织。释放肾脏后,使用双手术结在肾血管和输尿管周围系上 Foro 丝线。等待大约 30 秒,直到肾脏变黑。然后用光滑的弯曲镊子握住它,并使用弯曲的剪刀从结的远端切割将其取出。使用浸有盐水的无菌棉签将剩余的肾蒂轻轻推回腹膜后空间,然后使用缝合线和夹子闭合肌肉和皮肤层。典型生存率和肾功能测量是在可逆性单侧输尿管梗阻后 84 天进行的。功能研究比较了可逆性单侧输尿管梗阻与单独肾切除术在缺水 18 小时后血尿素氮、透皮肾小球滤过率和尿渗透压方面的影响。在同一时间点,尿渗透压值明显低于肾切除术对照小鼠。

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