Li Jia-Long, Kwan Kristine J S, Lin Xue-Guang, Wang Jie, Chen Bo, Lu Yi-Jie, Wang Bo, Xie Shi-Shuai, Zhou Jiong, Yu Bo, Deng Ying, Jiang Shuai, Tang Jing-Dong
Department of Vascular Surgery, Fudan University Pudong Medical Center, Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai, 201399, China.
Thromb J. 2024 Jul 29;22(1):69. doi: 10.1186/s12959-024-00638-z.
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.
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).
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.
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.
血栓闭塞性脉管炎（TAO）因其罕见性及治疗效果不尽人意，在临床上仍具有挑战性。本研究旨在描述一种与TAO更为相似的新型TAO兔模型。
36只新西兰兔接受手术，将校准的明胶海绵颗粒（CGSPs）植入其右股动脉。CGSPs浸泡在不同溶液中以模拟不同类型的血栓：正常（NT；生理盐水）；炎性TAO血栓（TAO；二甲基亚砜[DMSO]），以及含甲氨蝶呤（MTX）的DMSO。所有组在第0天（即刻）、第1周（急性）、第2周（亚急性）和第4周（慢性）时间点接受临床评估、数字减影血管造影（DSA）和组织病理学分析。
TAO兔在第4周出现右趾缺血迹象。在DSA上，TAO兔从第1周开始出现螺旋状侧支循环形成。在苏木精-伊红（H&E）染色中，第1周观察到CGSP逐渐降解，同时红细胞聚集增加和炎性细胞迁移。第2周，观察到中膜层紊乱和血管平滑肌细胞（VSMC）增殖。在TAO兔中，迁移的VSMC、炎性细胞和含有胶原样物质的细胞外基质逐渐阻塞管腔。第4周，TAO兔的动脉管腔充满相对有序的VSMC和内皮细胞簇，炎性细胞较少。在MTX治疗组中发现了新生血管形成。
新型TAO兔模型在临床、影像学和组织病理学上与人类TAO更为相似。TAO模型中IT进展的组织学分析表明其起源于VSMC。
