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心脏 N-甲基-D-天冬氨酸受体在心脏预处理中的作用——对心功能和氧化应激的影响。

The Role of Cardiac N-Methyl-D-Aspartate Receptors in Heart Conditioning-Effects on Heart Function and Oxidative Stress.

机构信息

Department of Human Pathophysiology, I.M. Sechenov First Moscow State Medical University, Trubetskaya str. 2, 119992 Moscow, Russia.

Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia.

出版信息

Biomolecules. 2020 Jul 16;10(7):1065. doi: 10.3390/biom10071065.

Abstract

As well as the most known role of N-methyl-D-aspartate receptors (NMDARs) in the nervous system, there is a plethora of evidence that NMDARs are also present in the cardiovascular system where they participate in various physiological processes, as well as pathological conditions. The aim of this study was to assess the effects of preconditioning and postconditioning of isolated rat heart with NMDAR agonists and antagonists on heart function and release of oxidative stress biomarkers. The hearts of male Wistar albino rats were subjected to global ischemia for 20 min, followed by 30 min of reperfusion, using the Langendorff technique, and cardiodynamic parameters were determined during the subsequent preconditioning with the NMDAR agonists glutamate (100 µmol/L) and (RS)-(Tetrazol-5-yl)glycine (5 μmol/L) and the NMDAR antagonists memantine (100 μmol/L) and MK-801 (30 μmol/L). In the postconditioning group, the hearts were perfused with the same dose of drugs during the first 3 min of reperfusion. The oxidative stress biomarkers were determined spectrophotometrically in samples of coronary venous effluent. The NMDAR antagonists, especially MK-801, applied in postconditioning had a marked antioxidative effect with a most pronounced protective effect. The results from this study suggest that NMDARs could be a potential therapeutic target in the prevention and treatment of ischemic and reperfusion injury of the heart.

摘要

除了 N-甲基-D-天冬氨酸受体 (NMDAR) 在神经系统中最广为人知的作用外,还有大量证据表明 NMDAR 也存在于心血管系统中,它们参与各种生理过程以及病理状况。本研究旨在评估使用 NMDAR 激动剂和拮抗剂对分离大鼠心脏进行预处理和后处理对心脏功能和氧化应激生物标志物释放的影响。使用 Langendorff 技术,雄性 Wistar 白化大鼠的心脏经历 20 分钟的整体缺血,随后进行 30 分钟的再灌注,并在随后使用 NMDAR 激动剂谷氨酸 (100 μmol/L) 和 (RS)-(四唑-5-基)甘氨酸 (5 μmol/L) 进行预处理时确定心脏动力学参数,和 NMDAR 拮抗剂美金刚 (100 μmol/L) 和 MK-801 (30 μmol/L)。在后处理组中,在再灌注的前 3 分钟用相同剂量的药物灌注心脏。通过分光光度法在冠状静脉流出物样本中测定氧化应激生物标志物。在预处理中应用的 NMDAR 拮抗剂,特别是 MK-801,具有明显的抗氧化作用,具有最显著的保护作用。本研究的结果表明,NMDAR 可能是预防和治疗心脏缺血再灌注损伤的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd3d/7408261/b74a0721227d/biomolecules-10-01065-g001.jpg

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