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用于检测与肠道再灌注损伤相关的活性氧和氮物种的荧光分子探针的转化应用

Translational Application of Fluorescent Molecular Probes for the Detection of Reactive Oxygen and Nitrogen Species Associated with Intestinal Reperfusion Injury.

作者信息

de Holanda Gustavo Sampaio, Dos Santos Valença Samuel, Carra Amabile Maran, Lichtenberger Renata Cristina Lopes, de Castilho Bianca, Franco Olavo Borges, de Moraes João Alfredo, Schanaider Alberto

机构信息

Centre of Experimental Surgery, Post Graduate Program in Surgical Sciences, Department of Surgery, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 219491-590, Brazil.

Redox Biology Laboratory, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.

出版信息

Metabolites. 2021 Nov 26;11(12):802. doi: 10.3390/metabo11120802.

Abstract

Acute mesenteric ischemia, caused by an abrupt interruption of blood flow in the mesenteric vessels, is associated with high mortality. When treated with surgical interventions or drugs to re-open the vascular lumen, the reperfusion process itself can inflict damage to the intestinal wall. Ischemia and reperfusion injury comprise complex mechanisms involving disarrangement of the splanchnic microcirculatory flow and impairment of the mitochondrial respiratory chain due to initial hypoxemia and subsequent oxidative stress during the reperfusion phase. This pathophysiologic process results in the production of large amounts of reactive oxygen (ROS) and nitrogen (RNS) species, which damage deoxyribonucleic acid, protein, lipids, and carbohydrates by autophagy, mitoptosis, necrosis, necroptosis, and apoptosis. Fluorescence-based systems using molecular probes have emerged as highly effective tools to monitor the concentrations and locations of these often short-lived ROS and RNS. The timely and accurate detection of both ROS and RNS by such an approach would help to identify early injury events associated with ischemia and reperfusion and increase overall clinical diagnostic sensitivity. This abstract describes the pathophysiology of intestinal ischemia and reperfusion and the early biological laboratory diagnosis using fluorescent molecular probes anticipating clinical decisions in the face of an extremely morbid disease.

摘要

急性肠系膜缺血由肠系膜血管血流突然中断引起,死亡率很高。在采用手术干预或药物重新开通血管腔进行治疗时,再灌注过程本身会对肠壁造成损伤。缺血再灌注损伤包含复杂机制,涉及内脏微循环血流紊乱以及再灌注阶段因初始低氧血症和随后的氧化应激导致的线粒体呼吸链损伤。这种病理生理过程会产生大量活性氧(ROS)和活性氮(RNS),它们通过自噬、线粒体凋亡、坏死、坏死性凋亡和凋亡作用损害脱氧核糖核酸、蛋白质、脂质和碳水化合物。使用分子探针的基于荧光的系统已成为监测这些通常寿命短暂的ROS和RNS浓度及位置的高效工具。通过这种方法及时准确地检测ROS和RNS,将有助于识别与缺血再灌注相关的早期损伤事件,并提高整体临床诊断敏感性。本摘要描述了肠道缺血再灌注的病理生理学以及使用荧光分子探针进行早期生物学实验室诊断,以期为面对这种极严重疾病时的临床决策提供依据。

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