Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
First Department of Propaedeutic Surgery, Hippocration General Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Sci Rep. 2020 Mar 19;10(1):5040. doi: 10.1038/s41598-020-61268-9.
Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p < 0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocking key protective signaling routes abrogated the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-β1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-β1 as an attractive target for manipulation in this context.
在腹主动脉瘤 (AAA) 修复过程中，对肾上主动脉进行夹闭会导致局部（即肾脏）和远处（即心脏）组织发生缺血再灌注损伤 (IRI)。为了研究减轻 IRI 诱导的组织损伤的围手术期方法，Wistar 大鼠仅接受肾上主动脉夹闭，或在夹闭前后结合短暂的缺血预处理，或同时进行这两种操作。血清分析显示，与对照组相比，预处理组的关键生化参数显著降低，反映出全身水平的组织损伤减少和肾功能改善（p < 0.05），这一结果得到了组织病理学评估的证实。重要的是，作为 DNA 损伤标志物的 8-oxo-G、γH2AX 和 pATM 的水平在预处理组中较非预处理组降低。在这种情况下，心肌中 NADPH 氧化酶（自由基的来源）减少。值得注意的是，阻断关键保护信号通路的 5-HD 和 8-SPT 给药会消除预处理的有益作用。为了进一步了解 IRI 对心脏的非靶向影响，研究人员注意到，在预处理组中，血清 TGF-β1 水平降低，而在给予 5-HD 和 8-SPT 后，这种差异消失。总之，预处理策略可减少肾脏和心肌损伤。此外，本研究强调 TGF-β1 作为该背景下的一个有吸引力的调控靶点。
