Al-Salam Suhail, Hashmi Satwat
Department of Pathology, College of medicine and health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Department of Biological and Biomedical Sciences, Agha Khan University, Karachi, Pakistan.
Cell Physiol Biochem. 2018;50(3):1123-1139. doi: 10.1159/000494539. Epub 2018 Oct 24.
BACKGROUND/AIMS: Myocardial reperfusion has the potential to salvage the ischemic myocardium after a period of coronary occlusion. Reperfusion, however, can cause a wide spectrum of deleterious effects. Galectin-3 (GAL-3), a beta galactoside binding lectin, is closely associated with myocardial infarction (MI), myocardial fibrosis and heart failure. In our study, we investigated its role in ischemia-reperfusion injuries (IR) as this phenomenon is extremely relevant to the early intervention after acute MI.
C57B6/J wild type (WT) mice and GAL-3 knockout (KO) mice were used for murine model of IR injury in the heart where a period of 30 minutes ischemia was followed by 24 hours of reperfusion. Heart samples were processed for immunohistochemical and immunofluorescent labeling, morphometric analysis, western blot and enzyme-linked immunosorbent assay to identify the apoptotic, inflammatory and oxidative stress role of GAL-3.
Our results show that there was a significant increase in GAL-3 levels in the heart which shows GAL-3 is playing a role in the ischemia reperfusion injury. Troponin I was also significantly higher in GAL-3-KO group than wild type. Our study shows that GAL-3 is associated with an increase in the antioxidant activity in the IR injured myocardium. Antioxidant enzymes superoxide dismutase, glutathione and catalase were found to be significantly raised in the GAL-3 wild type IR as compared to the GAL-3 KO IR group. A significant increase in apoptotic activity is seen in GAL-3 KO IR group as compared with GAL-3 wild IR group.
Our study shows that GAL-3 can affect the redox pathways, controlling cell survival and death, and plays a protective role on the myocardium following IR injury.
背景/目的:心肌再灌注有可能挽救冠状动脉闭塞一段时间后的缺血心肌。然而,再灌注会导致一系列有害影响。半乳糖凝集素-3(GAL-3)是一种β-半乳糖苷结合凝集素,与心肌梗死(MI)、心肌纤维化和心力衰竭密切相关。在我们的研究中,我们研究了其在缺血再灌注损伤(IR)中的作用,因为这种现象与急性心肌梗死后的早期干预极为相关。
使用C57B6/J野生型(WT)小鼠和GAL-3基因敲除(KO)小鼠建立心脏IR损伤小鼠模型,先进行30分钟的缺血,然后进行24小时的再灌注。对心脏样本进行免疫组织化学和免疫荧光标记、形态计量分析、蛋白质印迹和酶联免疫吸附测定,以确定GAL-3在凋亡、炎症和氧化应激中的作用。
我们的结果表明,心脏中GAL-3水平显著升高,表明GAL-3在缺血再灌注损伤中发挥作用。GAL-3基因敲除组的肌钙蛋白I也显著高于野生型。我们的研究表明,GAL-3与IR损伤心肌中抗氧化活性的增加有关。与GAL-3基因敲除的IR组相比,GAL-3野生型IR组中的抗氧化酶超氧化物歧化酶、谷胱甘肽和过氧化氢酶显著升高。与GAL-3野生型IR组相比,GAL-3基因敲除的IR组中凋亡活性显著增加。
我们的研究表明,GAL-3可以影响氧化还原途径,控制细胞存活和死亡,并在IR损伤后对心肌发挥保护作用。