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一种用于研究人类肾脏冷冻消融的新型鼠类模型。

A novel murine model for the study of human renal cryoablation.

机构信息

Division of Urology/Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

出版信息

BJU Int. 2007 Dec;100(6):1372-6. doi: 10.1111/j.1464-410X.2007.07102.x.

DOI:10.1111/j.1464-410X.2007.07102.x
PMID:17850388
Abstract

OBJECTIVE

to develop a reproducible, non-debilitating in vivo murine model of human renal cryoablation using a standard closed argon-delivery system.

MATERIALS AND METHODS

Custom engineered 2-mm conical tip cryoprobes for use on the standard argon-based cryoablation unit (Endocare, Inc. Irvine, CA, USA) were used to create small controllable iceballs (−160 °C) in the mouse kidney. The time to create a 4-mm cryolesion was compared using a contact vs puncture technique in 10 mice. To show consistency of the induced-freeze injury, a 4-mm iceball was created in 20 murine renal units and the time to creation and the size of the resultant cryolesion measured. To investigate lesion regression and histological changes, we created a 4-mm renal cryolesion in 28 mice and killed four each at 1, 3, 7, 14, 21, 28, and 35 days. The measured coronal cross-sectional area of the cryoablation site at necroscopy was compared to the initial calculated area as a percentage. To assess renal preservation, blood urea nitrogen (BUN) and creatinine levels at 1 week after cryoablation or sham ablation was compared (10 mononephric mice in each group).

RESULTS

The time to create the desired iceball was 1.9 times quicker using the puncture vs the contact technique. The mean (sd) time to forming a 4-mm iceball was 35.3 (4.8) s with a mean maximum length of the resultant post-thaw injury of 5.7 (0.5) mm and a 9% coefficient of variance. Regression analysis of the two-dimensional cross-sectional coronal area of the cryolesion showed a statistically significant linear pattern of regression over time (P = 0.037) and classic histological findings. There was no significant difference in the BUN or creatinine levels in mononephric mice 1 week after cryotherapy compared with the sham-ablated controls.

CONCLUSIONS

We describe a reproducible, non-debilitating, easily manipulated murine model for the study of human renal cryoablation.

摘要

目的

使用标准封闭氩气输送系统,开发一种可重现、非致残的人类肾脏冷冻消融活体小鼠模型。

材料与方法

定制设计的用于标准氩基冷冻消融设备(美国加利福尼亚州欧文市 Endocare 公司)的 2 毫米锥形尖端冷冻探针,用于在小鼠肾脏中创建可控的小冰球(-160°C)。在 10 只小鼠中,比较了使用接触式和穿刺式技术创建 4 毫米冷冻消融区的时间。为了证明诱导性冷冻损伤的一致性,在 20 个鼠肾单位中创建了 4 毫米冰球,并测量了创建时间和产生的冷冻消融区的大小。为了研究病变消退和组织学变化,我们在 28 只小鼠中创建了 4 毫米肾脏冷冻消融区,每 4 只分别在 1、3、7、14、21、28 和 35 天处死。在尸检时测量的冷冻消融部位的冠状横截面面积与初始计算面积的百分比进行比较。为了评估肾脏保存,比较了冷冻消融或假手术 1 周后血尿素氮(BUN)和肌酐水平(每组 10 只单肾小鼠)。

结果

与接触式技术相比,使用穿刺式技术创建所需冰球的时间快 1.9 倍。形成 4 毫米冰球的平均(标准差)时间为 35.3(4.8)秒,解冻后最大损伤长度的平均值为 5.7(0.5)毫米,变异系数为 9%。冷冻消融区二维冠状横截面面积的回归分析显示,随着时间的推移,回归呈显著线性模式(P = 0.037),且具有典型的组织学发现。与假手术对照组相比,冷冻治疗后 1 周的单肾小鼠的 BUN 或肌酐水平没有显著差异。

结论

我们描述了一种可重现、非致残、易于操作的人类肾脏冷冻消融活体小鼠模型。

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