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能够更好模拟人类主动脉瘤疾病的扩张直径的兔主动脉瘤模型。

Rabbit aortic aneurysm model with enlarging diameter capable of better mimicking human aortic aneurysm disease.

机构信息

Department of Interventional Radiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Histology&Embryology, Medical College of Zhengzhou University; Department of Ultrasound, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

出版信息

PLoS One. 2018 Jun 11;13(6):e0198818. doi: 10.1371/journal.pone.0198818. eCollection 2018.

Abstract

The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group. Aneurysm group rabbits underwent extrinsic aortic stenosis below the right renal artery and received a 10-minute incubation of 60 μl elastase (1 unit/μl). Absorbable suture was used in Group A and nonabsorbable cotton thread was used in Group B. A sham operation was performed in the SHAM group. Aortic diameter was measured after 1, 3, 7, and 15 weeks; thereafter animals were sacrificed for histopathological, immunohistochemical and quantitative studies. Two rabbits died at 29 and 48 days, respectively, after operation in Group B. All aneurysms formed and enlarged progressively by 3 weeks in the Aneurysm groups. However, diameter enlargement in Group A was significantly lower than that in Group B at 7 weeks. Aneurysm groups developed intimal hyperplasia; intima-media thickness (IMT) increased significantly by week 7, and aortic media thickness and intima-media ratio (IMR) increased significantly by week 15. Marked destruction of elastin fibers and smooth muscle cells (SMCs) occurred 1 week later and increased progressively thereafter. Intimal hyperplasia and SMCs content in Group A increased significantly by week 15 compared with Group B. Aneurysm groups exhibited strong expression of matrix metalloproteinases 2 and 9 and RAM11 by week 1, and decreased progressively thereafter. In conclusion, this novel rabbit AAA model enlarges progressively without coarctation and is capable of better mimicking human aortic aneurysm disease.

摘要

自愈合现象可在弹性蛋白酶诱导的腹主动脉瘤(AAA)模型中发现,而缩窄可成功诱导 AAA 增大。不幸的是,这些增大模型中的主动脉缩窄在人类 AAA 疾病中一般不存在。本研究旨在建立一种更好模拟人类主动脉瘤疾病的兔增大 AAA 实验模型。84 只雄性新西兰白兔随机分为三组:两组动脉瘤组(A 组和 B 组)和一组假手术组(SHAM 组)。动脉瘤组兔在右肾动脉以下进行外源性主动脉狭窄,并接受 60μl 弹性蛋白酶(1 单位/μl)孵育 10 分钟。A 组使用可吸收缝线,B 组使用不可吸收棉线。SHAM 组进行假手术。术后 1、3、7 和 15 周测量主动脉直径;此后处死动物进行组织病理学、免疫组织化学和定量研究。B 组有 2 只兔子分别于术后 29 天和 48 天死亡。两组动脉瘤均在 3 周内形成并逐渐增大。然而,7 周时 A 组的直径增大明显低于 B 组。动脉瘤组均发生内膜增生;内膜中层厚度(IMT)在第 7 周显著增加,主动脉中层厚度和内膜中层比(IMR)在第 15 周显著增加。弹性纤维和平滑肌细胞(SMCs)的明显破坏在 1 周后发生,并在此后逐渐增加。15 周时 A 组的内膜增生和 SMCs 含量明显高于 B 组。动脉瘤组在第 1 周表现出基质金属蛋白酶 2 和 9 以及 RAM11 的强表达,此后逐渐降低。总之,这种新型兔 AAA 模型在没有缩窄的情况下逐渐增大,能够更好地模拟人类主动脉瘤疾病。

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