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通过局部弹性蛋白酶和口服 β-氨基丙腈联合作用在小鼠中建立高级腹部主动脉瘤模型。

Advanced Abdominal Aortic Aneurysm Modeling in Mice by Combination of Topical Elastase and Oral ß-aminopropionitrile.

机构信息

Division of Vascular Surgery, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health;

Division of Vascular Surgery and Endovascular Therapy, University of Florida College of Medicine.

出版信息

J Vis Exp. 2024 Jul 26(209). doi: 10.3791/66812.

DOI:10.3791/66812
PMID:39141527
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11852951/
Abstract

The topical elastase murine model of abdominal aortic aneurysm (AAA) is enhanced when combined with ß-aminopropionitrile (BAPN)-supplemented drinking water to reliably produce true infrarenal aneurysms with behaviors that mimic human AAAs. Topically applying elastase to the adventitia of the infrarenal aorta causes structural damage to the elastic layers of the aortic wall and initiates aneurysmal dilation. Co-administering BAPN, a lysyl oxidase inhibitor, promotes sustained wall degeneration by reducing collagen and elastin crosslinking. This combination results in large AAAs that progressively expand, form intraluminal thrombus, and are capable of rupture. Refining surgical techniques, such as circumferentially isolating the entire infrarenal aortic segment, can help standardize the procedure for a consistent and thorough application of porcine pancreatic elastase despite different operators and anatomic variations between mice. Therefore, the elastase/BAPN model is a refined approach to surgically inducing AAA in mice, which may better recapitulate human aneurysms and provide additional opportunities to study aneurysm growth and rupture risk.

摘要

弹性蛋白酶/β-氨基丙腈(BAPN)联合诱导的小鼠腹主动脉瘤(AAA)模型是一种经典的、可增强的模型,它能够可靠地诱导出真正的肾下型 AAA,并具有与人类 AAA 相似的行为特征。将弹性蛋白酶局部应用于肾下主动脉的外膜,会导致主动脉壁的弹性层结构损伤,并引发动脉瘤样扩张。同时给予 BAPN(赖氨酰氧化酶抑制剂)可通过减少胶原蛋白和弹性蛋白的交联,促进持续的壁退化。这种联合作用导致大型 AAA 逐渐扩张、形成管腔内血栓,并可能发生破裂。改进手术技术,如环形分离整个肾下主动脉段,可以帮助标准化手术过程,尽管操作人员和小鼠之间的解剖差异,仍能确保猪胰腺弹性蛋白酶的充分应用。因此,弹性蛋白酶/BAPN 模型是一种改良的方法,可在小鼠中诱导 AAA,它可能更好地模拟人类的动脉瘤,并提供更多机会来研究动脉瘤的生长和破裂风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/11852951/a050b894a465/nihms-2048733-f0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/11852951/049ed4328ff7/nihms-2048733-f0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/11852951/a050b894a465/nihms-2048733-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/11852951/227555b51c0b/nihms-2048733-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/11852951/f704efca053c/nihms-2048733-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/11852951/2858489b72cf/nihms-2048733-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/11852951/049ed4328ff7/nihms-2048733-f0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0472/11852951/64a35b00a233/nihms-2048733-f0006.jpg
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本文引用的文献

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Identifying novel mechanisms of abdominal aortic aneurysm unbiased proteomics and systems biology.通过无偏蛋白质组学和系统生物学鉴定腹主动脉瘤的新机制
Front Cardiovasc Med. 2022 Aug 3;9:889994. doi: 10.3389/fcvm.2022.889994. eCollection 2022.
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Mouse Abdominal Aortic Aneurysm Model Induced by Perivascular Application of Elastase.
血管周应用弹性蛋白酶诱导的小鼠腹主动脉瘤模型。
J Vis Exp. 2022 Feb 11(180). doi: 10.3791/63608.
4
Experimental aortic aneurysm severity and growth depend on topical elastase concentration and lysyl oxidase inhibition.实验性主动脉瘤的严重程度和生长取决于局部弹性蛋白酶浓度和赖氨酰氧化酶抑制。
Sci Rep. 2022 Jan 7;12(1):99. doi: 10.1038/s41598-021-04089-8.
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Translating mouse models of abdominal aortic aneurysm to the translational needs of vascular surgery.将腹主动脉瘤小鼠模型转化为血管外科的转化需求。
JVS Vasc Sci. 2021 Mar 3;2:219-234. doi: 10.1016/j.jvssci.2021.01.002. eCollection 2021.
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Epidemiology of endovascular and open repair for abdominal aortic aneurysms in the United States from 2004 to 2015 and implications for screening.2004 年至 2015 年美国腹主动脉瘤腔内和开放修复的流行病学及筛查意义。
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