Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
Shaanxi Key Laboratory of Natural Products & Chemical Biology, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, China.
Eur J Pharmacol. 2019 Nov 15;863:172701. doi: 10.1016/j.ejphar.2019.172701. Epub 2019 Sep 27.
Myocardial ischemia/reperfusion (IR) injury is caused by the restoration of the coronary blood flow following an ischemic episode. Accumulating evidence suggests that galectin-3, a β-galactoside-binding lectin, acts as a biomarker in heart disease. However, it remains unclear whether manipulating galectin-3 affects the susceptibility of the heart to IR injury. In this study, RNA sequencing (RNA-seq) analysis identified that Lgals3 (galecin-3) plays an indispensable role in IR-induced cardiac damage. Immunostaining and immunoblot assays confirmed that the expression of galectin-3 was markedly increased in myocardial IR injury both in vivo and in vitro. Echocardiographic analysis showed that cardiac dysfunction in experimental IR injury was significantly attenuated by galectin-3 inhibitors including pectin (1%, i.p.) from citrus and binding peptide G3-C12 (5.0 mg/kg, i.p.). Galectin-3 inhibitor-treated mice exhibited smaller infarct sizes and decreased tissue injury. Furthermore, TUNEL staining showed that galectin-3 inhibition suppressed IR-mediated cardiomyocyte apoptosis. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) levels were well-preserved and IR-induced changes of mitochondrial cyto c, cytosol cyto c, caspase-9, caspase-3, Bcl-2 and Bax in the galectin-3 inhibitor-treated groups were observed. Our findings indicate that the pathological upregulation of galectin-3 contributes to IR-induced cardiac dysfunction and that galectin-3 inhibition ameliorates myocardial injury, highlighting its therapeutic potential.
心肌缺血/再灌注 (IR) 损伤是由缺血事件后冠状动脉血流恢复引起的。越来越多的证据表明，半乳糖凝集素-3（一种 β-半乳糖苷结合凝集素）作为心脏病的生物标志物发挥作用。然而，目前尚不清楚操纵半乳糖凝集素-3 是否会影响心脏对 IR 损伤的易感性。在这项研究中，RNA 测序 (RNA-seq) 分析表明 Lgals3（半乳糖凝集素-3）在 IR 诱导的心脏损伤中起着不可或缺的作用。免疫染色和免疫印迹分析证实，半乳糖凝集素-3的表达在体内和体外的心肌 IR 损伤中均明显增加。超声心动图分析表明，半乳糖凝集素-3 抑制剂（包括柑橘中的果胶（1%，腹腔内注射）和结合肽 G3-C12（5.0mg/kg，腹腔内注射））显著减轻实验性 IR 损伤中的心脏功能障碍。半乳糖凝集素-3 抑制剂治疗的小鼠梗死面积较小，组织损伤减少。此外，TUNEL 染色表明，半乳糖凝集素-3 抑制抑制了 IR 介导的心肌细胞凋亡。线粒体膜电位 (MMP) 和线粒体通透性转换孔 (mPTP) 水平得到很好的维持，并且在半乳糖凝集素-3 抑制剂治疗组中观察到 IR 诱导的线粒体细胞色素 c、细胞质细胞色素 c、半胱天冬酶-9、半胱天冬酶-3、Bcl-2 和 Bax 的变化。我们的研究结果表明，半乳糖凝集素-3 的病理性上调导致 IR 诱导的心脏功能障碍，半乳糖凝集素-3 抑制可改善心肌损伤，突出了其治疗潜力。
