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锌-阿司匹林预处理可减轻血管重建大鼠模型中动脉移植物的内皮损伤。

Zinc-aspirin preconditioning reduces endothelial damage of arterial grafts in a rodent model of revascularization.

作者信息

Benke Kálmán, Stengl Roland, Stark Klára Aliz, Bai Yang, Radovits Tamás, Loganathan Sivakkanan, Korkmaz-Icöz Sevil, Csonka Máté, Karck Matthias, Szabó Gábor, Veres Gábor

机构信息

Department of Cardiac Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.

Heart and Vascular Center, Semmelweis University, Budapest, Hungary.

出版信息

Front Cardiovasc Med. 2024 Jan 4;10:1288128. doi: 10.3389/fcvm.2023.1288128. eCollection 2023.

Abstract

INTRODUCTION

Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. The prognosis of revascularization via CABG is determined by the patency of the used grafts, for which an intact endothelium is essential. The degree of ischemia-reperfusion injury (IRI), which occurs during the harvest and implantation of the grafts, is an important determinant of graft patency. Preconditioning with aspirin, a nonsteroidal anti-inflammatory drug has been shown to reduce the functional and molecular damage of arterial grafts in a rodent model. Studies have found that the zinc-aspirin complex may be able to exert an even better protective effect in pathological cardiovascular conditions. Thus, our aim was to characterize the protective effect of zinc-aspirin complex on free arterial grafts in a rodent model of revascularization.

METHODS

Donor Lewis rats were treated with either zinc-aspirin, aspirin, or placebo ( = 8) for 5 days, then the aortic arches were harvested and stored in cold preservation solution and implanted heterotopically in the abdominal cavity of the recipient rats, followed by 2 h of reperfusion. There was also a non-ischemia-reperfusion control group ( = 8). Functional measurements using organ bath and histomorphological changes using immunohistochemistry were analyzed.

RESULTS

The endothelium dependent maximal vasorelaxation was improved (non-transplanted control group: 82% ± 3%, transplanted control group: 14% ± 2%, aspirin group: 31% ± 4%, zinc-aspirin group: 52% ± 4%), the nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the groups preconditioned with aspirin or zinc-aspirin. However, zinc-aspirin proved to be more effective in the reduction of IRI, than aspirin alone.

DISCUSSION

Preconditioning with zinc-aspirin could be a promising way to protect the function and structural integrity of free arterial grafts, thus improving the outcomes of CABG.

摘要

引言

冠状动脉旁路移植术(CABG)是最常见的心脏外科手术。通过CABG进行血运重建的预后取决于所用移植物的通畅情况,而完整的内皮对于移植物通畅至关重要。在移植物获取和植入过程中发生的缺血再灌注损伤(IRI)程度是移植物通畅的重要决定因素。在啮齿动物模型中,使用非甾体抗炎药阿司匹林进行预处理已显示可减少动脉移植物的功能和分子损伤。研究发现,锌 - 阿司匹林复合物在病理性心血管疾病中可能能够发挥更好的保护作用。因此,我们的目的是在啮齿动物血运重建模型中表征锌 - 阿司匹林复合物对游离动脉移植物的保护作用。

方法

将供体Lewis大鼠用锌 - 阿司匹林、阿司匹林或安慰剂(每组 = 8只)处理5天,然后获取主动脉弓并保存在冷保存溶液中,异位植入受体大鼠的腹腔,随后进行2小时的再灌注。还有一个非缺血再灌注对照组(每组 = 8只)。分析了使用器官浴进行的功能测量和使用免疫组织化学进行的组织形态学变化。

结果

内皮依赖性最大血管舒张功能得到改善(未移植对照组:82% ± 3%,移植对照组:14% ± 2%,阿司匹林组:31% ± 4%,锌 - 阿司匹林组:52% ± 4%),硝基氧化应激和细胞凋亡减少,并且在使用阿司匹林或锌 - 阿司匹林预处理的组中显示出显著的内皮保护作用。然而,锌 - 阿司匹林在减少IRI方面比单独使用阿司匹林更有效。

讨论

用锌 - 阿司匹林预处理可能是保护游离动脉移植物功能和结构完整性的一种有前景的方法,从而改善CABG的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac94/10794572/c85d9b8dfdd0/fcvm-10-1288128-g001.jpg

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