Durmaz Selim, Kurtoğlu Tünay, Rahman Ömer Faruk, Tataroğlu Canten, Yılmaz Mustafa, Barbarus Emin, Erkan Muhammet Hüseyin
Department of Cardiovascular Surgery, Adnan Menderes University Faculty of Medicine, Aydın, Türkiye.
Department of Medical Pathology, Adnan Menderes University Faculty of Medicine, Aydın, Türkiye.
Turk Gogus Kalp Damar Cerrahisi Derg. 2022 Apr 27;30(2):184-191. doi: 10.5606/tgkdc.dergisi.2022.22831. eCollection 2022 Apr.
This study aims to investigate the effects of different direct oral anticoagulants on experimental renal injury induced by temporary infrarenal aortic occlusion.
A total of 35 male Wistar rats (250 to 350 g) were randomly allocated to any of the five groups: sham, ischemia-reperfusion, rivaroxaban, dabigatran, and apixaban groups. Sham group underwent median laparotomy. Ischemia-reperfusion group was given saline gavage for one week. Animals in the other groups received rivaroxaban (3 mg/kg), dabigatran (15 mg/kg), or apixaban (10 mg/kg) daily once for one week via oral gavage. The infrarenal abdominal aorta was clamped for 60 min, and reperfusion was maintained for 120 min in the ischemia-reperfusion, rivaroxaban, dabigatran, and apixaban groups. At the end of reperfusion, kidneys were harvested for biochemical and histopathological analysis.
Renal total antioxidant capacity was reduced, and total oxidant status, interleukin-1 beta, and tumor necrosis factor-alpha were elevated in the ischemia-reperfusion group, compared to the sham group (p<0.005). Histological damage scores were also higher in the ischemia-reperfusion group (p<0.005). Administration of direct oral anticoagulants caused an increase of total antioxidant capacity and reduction of total oxidant status, tumor necrosis factor-alpha, and interleukin-1 beta in the rivaroxaban, dabigatran, and apixaban groups compared to the ischemia-reperfusion group (p<0.005). Histological damage scores were lower in the rivaroxaban and dabigatran groups than the ischemia-reperfusion group scores (p<0.005).
Direct oral anticoagulants reduce aortic clamping-induced renal tissue oxidation and inflammation. Rivaroxaban and dabigatran attenuate ischemia-reperfusion-related histological damage in kidneys.
本研究旨在探讨不同直接口服抗凝剂对暂时性肾下腹主动脉闭塞所致实验性肾损伤的影响。
总共35只雄性Wistar大鼠（250至350克）被随机分配到以下五组中的任意一组：假手术组、缺血再灌注组、利伐沙班组、达比加群组和阿哌沙班组。假手术组接受正中剖腹术。缺血再灌注组给予生理盐水灌胃一周。其他组的动物通过口服灌胃每日一次给予利伐沙班（3毫克/千克）、达比加群（15毫克/千克）或阿哌沙班（10毫克/千克），持续一周。在缺血再灌注组、利伐沙班组、达比加群组和阿哌沙班组中，肾下腹主动脉被夹闭60分钟，并维持再灌注120分钟。再灌注结束时，采集肾脏进行生化和组织病理学分析。
与假手术组相比，缺血再灌注组的肾总抗氧化能力降低，总氧化状态、白细胞介素-1β和肿瘤坏死因子-α升高（p<0.005）。缺血再灌注组的组织学损伤评分也更高（p<0.005）。与缺血再灌注组相比，利伐沙班组、达比加群组和阿哌沙班组给予直接口服抗凝剂后，总抗氧化能力增加，总氧化状态、肿瘤坏死因子-α和白细胞介素-1β降低（p<0.005）。利伐沙班组和达比加群组的组织学损伤评分低于缺血再灌注组评分（p<0.005）。
直接口服抗凝剂可减轻主动脉夹闭所致的肾组织氧化和炎症。利伐沙班和达比加群可减轻肾脏缺血再灌注相关的组织学损伤。
