Gencpınar Tugra, Bilen Cagatay, Kemahli Baris, Sayarer Ceren, Akokay Pinar, Bayrak Serdar, Erdal Cenk
Department of Cardiovascular Surgery, Dokuz Eylül University Faculty of Medicine, İzmir, Türkiye.
Department of Cardiovascular Surgery, Adnan Menderes University Faculty of Medicine, Aydın, Türkiye.
Turk Gogus Kalp Damar Cerrahisi Derg. 2024 Oct 30;32(4):378-386. doi: 10.5606/tgkdc.dergisi.2024.25890. eCollection 2024 Oct.
This study aimed to evaluate the effects of edoxaban, which is used in venous thrombosis, systemic embolism, and stroke, on an aortic aneurysm model and to demonstrate the pharmacokinetic and molecular effects of edoxaban through the induction of apoptosis.
In this double-blind experimental study, 21 Wistar albino male rats (mean weight: 290 g; range, 280 to 300 g) were divided into three groups: the sham group (n=7), the abdominal aortic aneurysm (AAA) group (n=7), and the AAA-edoxaban group (n=7). Edoxaban 10 mg/kg was given to the AAA-edoxaban group by oral gavage daily for 30 days. At the end of 30 days, the aneurysmal aorta was surgically removed and histologically examined. The abdominal aorta was surgically exposed and wrapped with a calcium chloride (0.5 mol/L) sponge for 10 min.
Immunohistochemically, aortic sections were marked with caspase-3 and caspase-9 antibodies. It was observed that the pathways that trigger apoptosis (caspase-3 and caspase-9; p <0.004 and p <0.005, respectively) were significantly reduced in the AAA-edoxaban group compared to the AAA group. In the AAA-edoxaban group, it was observed that the expansion in aortic diameter and the deterioration in the elastic fibril structure in the aortic aneurysm were decreased as a result of edoxaban treatment. Edoxaban treatment was observed to reduce cell death in both the tunica intima and tunica media.
This study provided strong evidence of the protective effect of edoxaban on aortic aneurysm-related vascular damage by reducing apoptosis and mitophagy.
本研究旨在评估用于静脉血栓形成、全身栓塞和中风的依度沙班对主动脉瘤模型的影响，并通过诱导细胞凋亡来证明依度沙班的药代动力学和分子效应。
在这项双盲实验研究中，将21只Wistar白化雄性大鼠（平均体重：290克；范围280至300克）分为三组：假手术组（n = 7）、腹主动脉瘤（AAA）组（n = 7）和AAA - 依度沙班组（n = 7）。依度沙班10毫克/千克通过口服灌胃给予AAA - 依度沙班组，每日一次，共30天。在30天结束时，手术切除动脉瘤样主动脉并进行组织学检查。手术暴露腹主动脉并用氯化钙（0.5摩尔/升）海绵包裹10分钟。
免疫组织化学分析中，主动脉切片用半胱天冬酶 - 3和半胱天冬酶 - 9抗体标记。观察到，与AAA组相比，AAA - 依度沙班组中触发细胞凋亡的途径（半胱天冬酶 - 3和半胱天冬酶 - 9；分别为p <0.004和p <0.005）显著减少。在AAA - 依度沙班组中，观察到依度沙班治疗使主动脉瘤的主动脉直径扩张和弹性纤维结构恶化减少。观察到依度沙班治疗可减少内膜和中膜的细胞死亡。
本研究提供了有力证据，证明依度沙班通过减少细胞凋亡和线粒体自噬对主动脉瘤相关血管损伤具有保护作用。
