Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China; Laboratory of Medical Imaging and Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Intervention and Department of Shenzhen Medical Intervention Engineering Center, The Second Clinical Medical College, Jinan University, Shenzhen, China.
J Vasc Surg. 2018 Jan;67(1):300-308.e2. doi: 10.1016/j.jvs.2016.12.120. Epub 2017 May 4.
Animal models are required to explore the mechanisms of and therapy for proximal descending thoracic aortic aneurysm (TAA). This study aimed to establish a reproducible swine model of proximal descending TAA that can further explain the occurrence and progression of proximal descending TAA.
Eighteen Chinese Wuzhishan miniature pigs (30.32 ± 1.34 kg) were randomized into the elastase group (n = 12) and the control group (n = 6). The elastase group received intra-adventitial injections of elastase (5 mL, 20 mg/mL), and the control group received injections of physiologic saline solution. A 4-cm descending thoracic aortic segment proximal to the left subclavian artery was isolated. The distance between the left subclavian artery and the injection starting point of the descending thoracic aorta was 0.5 cm. Elastic protease was circumferentially injected intra-adventitially into the isolated segment of the aortic wall in the elastase group by a handmade bent syringe. The length of the elastic protease injection was 2 cm. An average of 12 injection points were distributed in this 2-cm aortic segment. Each injection point used about 0.4 mL of elastic protease. The distance between two injection points was about 1.5 cm. All animals underwent digital subtraction angiography preoperatively and 3 weeks after operation. Three weeks after TAA induction, aortas were harvested for biochemical and histologic measurements.
All animals in the elastase group developed TAAs. No aneurysms were observed in the control group. The distance between the left subclavian artery and the TAA was 8.00 ± 4.19 mm. Preoperative and postoperative aortic diameters of the elastase group were 15.42 ± 0.43 mm and 24.53 ± 1.41 mm, respectively (P < .0001). Preoperative and postoperative aortic diameters of the control group were 15.31 ± 0.33 mm and 15.57 ± 0.40 mm, respectively (P = .5211). The changes of aortic structure and composition included reduction of smooth muscle cells and degradation of elastic fibers. Levels of matrix metalloproteinases 2 and 9 were increased in TAA tissue.
This study established a reproducible large animal model of proximal descending TAA. This model has the same biochemical characteristics as human aneurysms in the aspects of aortic expansion, aortic middle-level degeneration, and changes in the levels of matrix metalloproteinases and provides a platform for further study.
需要动物模型来探索近端降主动脉瘤（TAA）的发生机制和治疗方法。本研究旨在建立一种可重现的近端降主动脉 TAA 猪模型，以进一步解释近端降主动脉 TAA 的发生和进展。
将 18 头中国五指山小型猪（30.32±1.34kg）随机分为弹性蛋白酶组（n=12）和对照组（n=6）。弹性蛋白酶组接受胸主动脉外膜内注射弹性蛋白酶（5mL，20mg/mL），对照组接受生理盐水注射。分离左锁骨下动脉近端 4cm 的降主动脉段。左锁骨下动脉与降主动脉起始注射点之间的距离为 0.5cm。弹性蛋白酶组通过手工弯曲注射器将弹性蛋白酶环绕性注入主动脉壁的隔离段。弹性蛋白酶注射的长度为 2cm。在这个 2cm 的主动脉段中平均分布 12 个注射点。每个注射点使用约 0.4mL 的弹性蛋白酶。两个注射点之间的距离约为 1.5cm。所有动物在术前和术后 3 周均行数字减影血管造影检查。TAA 诱导后 3 周，采集主动脉进行生化和组织学测量。
弹性蛋白酶组的所有动物均发生了 TAA。对照组未见动脉瘤。左锁骨下动脉与 TAA 之间的距离为 8.00±4.19mm。弹性蛋白酶组术前和术后的主动脉直径分别为 15.42±0.43mm和 24.53±1.41mm（P<0.0001）。对照组术前和术后的主动脉直径分别为 15.31±0.33mm和 15.57±0.40mm（P=0.5211）。主动脉结构和成分的变化包括平滑肌细胞减少和弹性纤维降解。TAA 组织中基质金属蛋白酶 2 和 9 的水平升高。
本研究建立了一种可重现的近端降主动脉 TAA 大动物模型。该模型在主动脉扩张、中膜退变以及基质金属蛋白酶水平等方面与人动脉瘤具有相同的生化特征，为进一步研究提供了一个平台。
