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从实验台到临床:兔弹性蛋白酶诱导动脉瘤模型在颅内动脉瘤治疗临床前研究中的应用

From bench to bedside: utility of the rabbit elastase aneurysm model in preclinical studies of intracranial aneurysm treatment.

作者信息

Brinjikji Waleed, Ding Yong H, Kallmes David F, Kadirvel Ramanathan

机构信息

Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.

出版信息

J Neurointerv Surg. 2016 May;8(5):521-5. doi: 10.1136/neurintsurg-2015-011704. Epub 2015 Apr 22.

Abstract

Preclinical studies are important in helping practitioners and device developers improve techniques and tools for endovascular treatment of intracranial aneurysms. Thus an understanding of the major animal models used in such studies is important. The New Zealand rabbit elastase induced arterial aneurysm of the common carotid artery is one of the most commonly used models in testing the safety and efficacy of new endovascular devices. In this review we discuss: (1) the various techniques used to create the aneurysm, (2) complications of aneurysm creation, (3) natural history of the arterial aneurysm, (4) histopathologic and hemodynamic features of the aneurysm, (5) devices tested using this model, and (6) weaknesses of the model. We demonstrate how preclinical studies using this model are applied in the treatment of intracranial aneurysms in humans. The model has similar hemodynamic, morphological, and histologic characteristics to human aneurysms, and demonstrates similar healing responses to coiling as human aneurysms. Despite these strengths, however, the model does have many weaknesses, including the fact that the model does not emulate the complex inflammatory processes affecting growing and ruptured aneurysms. Furthermore, the extracranial location of the model affects its ability to be used in preclinical safety assessments of new devices. We conclude that the rabbit elastase model has characteristics that make it a simple and effective model for preclinical studies on the endovascular treatment of intracranial aneurysms, but further work is needed to develop aneurysm models that simulate the histopathologic and morphologic characteristics of growing and ruptured aneurysms.

摘要

临床前研究对于帮助从业者和设备开发者改进颅内动脉瘤血管内治疗的技术和工具非常重要。因此,了解此类研究中使用的主要动物模型很重要。新西兰兔弹性蛋白酶诱导的颈总动脉动脉瘤是测试新型血管内设备安全性和有效性时最常用的模型之一。在本综述中,我们讨论:(1)用于创建动脉瘤的各种技术,(2)动脉瘤创建的并发症,(3)动脉动脉瘤的自然病程,(4)动脉瘤的组织病理学和血流动力学特征,(5)使用该模型测试的设备,以及(6)该模型的弱点。我们展示了使用该模型的临床前研究如何应用于人类颅内动脉瘤的治疗。该模型具有与人类动脉瘤相似的血流动力学、形态学和组织学特征,并表现出与人类动脉瘤相似的对栓塞的愈合反应。然而,尽管有这些优点,该模型确实存在许多弱点,包括该模型无法模拟影响生长中和破裂动脉瘤的复杂炎症过程。此外,该模型位于颅外的位置影响了其在新设备临床前安全性评估中的应用能力。我们得出结论,兔弹性蛋白酶模型具有使其成为颅内动脉瘤血管内治疗临床前研究的简单有效模型的特征,但需要进一步开展工作来开发模拟生长中和破裂动脉瘤的组织病理学和形态学特征的动脉瘤模型。

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