The Buerger's rabbit model: a closer step to unravelling thromboangiitis obliterans?

IF 2.6 4区 医学 Q2 HEMATOLOGY Thrombosis Journal Pub Date : 2024-07-29 DOI:10.1186/s12959-024-00638-z
Jia-Long Li, Kristine J S Kwan, Xue-Guang Lin, Jie Wang, Bo Chen, Yi-Jie Lu, Bo Wang, Shi-Shuai Xie, Jiong Zhou, Bo Yu, Ying Deng, Shuai Jiang, Jing-Dong Tang
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Abstract

Objective: Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO.

Methods: Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic).

Results: The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group.

Conclusion: The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

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布尔格兔模型:向揭示血栓闭塞性脉管炎迈出的更近一步?
目的:血栓闭塞性脉管炎(TAO)由于其罕见性和治疗效果不佳,在临床上仍具有挑战性。本研究旨在描述一种新型 TAO 兔模型,该模型与 TAO 更为相似:方法:36 只新西兰兔通过手术将校准明胶海绵颗粒(CGSPs)植入右股动脉。CGSP浸泡在不同的溶液中,以模拟不同类型的血栓:正常血栓(NT;生理盐水);炎性TAO血栓(TAO;二甲基亚砜[DMSO]);以及含有甲氨蝶呤(MTX)的二甲基亚砜。所有组别都在第0天(即刻)、第1周(急性)、第2周(亚急性)和第4周(慢性)进行了临床评估、数字减影血管造影(DSA)和组织病理学分析:结果:TAO 兔在第 4 周出现右手指缺血症状。在 DSA 上,TAO 兔从第 1 周开始出现开瓶器状血管袢的形成。在 H&E 染色上,第 1 周观察到 CGSP 逐渐降解,红细胞聚集和炎性细胞迁移增加。第 2 周,观察到血管内膜中层紊乱和血管平滑肌细胞(VSMC)增殖。在 TAO 兔身上,移行的 VSMC、炎症细胞和含有胶原样物质的细胞外基质逐渐堵塞了管腔。第 4 周,TAO 兔的动脉管腔内充满了相对有序的 VSMC 和内皮细胞簇,炎性细胞较少。结论:结论:新型 TAO 兔模型在临床、影像学和组织病理学方面与人类 TAO 更为相似。对 TAO 模型中 IT 进展的组织学分析表明,它是由 VSMC 引起的。
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来源期刊
Thrombosis Journal
Thrombosis Journal Medicine-Hematology
CiteScore
3.80
自引率
3.20%
发文量
69
审稿时长
16 weeks
期刊介绍: Thrombosis Journal is an open-access journal that publishes original articles on aspects of clinical and basic research, new methodology, case reports and reviews in the areas of thrombosis. Topics of particular interest include the diagnosis of arterial and venous thrombosis, new antithrombotic treatments, new developments in the understanding, diagnosis and treatments of atherosclerotic vessel disease, relations between haemostasis and vascular disease, hypertension, diabetes, immunology and obesity.
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