Lin Cong, Wei Dazhen, Xin Dawei, Pan Jialin, Huang Mingyuan
Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, China.
Department of Intensive Care Unite, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, China.
J Toxicol Sci. 2019;44(6):425-433. doi: 10.2131/jts.44.425.
Cardiac fibroblasts (CFs) could be activated after myocardial infarction (MI). Thus, it is necessary to explore effective drugs to suppress the activation of CFs following MI. This study was designed to investigate the impacts of ellagic acid on CFs and the underlying mechanisms. The expression of histone deacetylases (HDACs) and fibrosis-related genes was detected by qRT-PCR and western blot. The Masson's Trichrome Staining assay was used to evaluate the area of cardiac fibrosis. The proliferation and migration of CFs were measured by CCK8 Kit and Transwell assay, respectively. Our results showed that ellagic acid significantly reduced protein expression of HDAC1, mRNA expression of collagen I, collagen III, MMP-2 and MMP-9 and the area of cardiac fibrosis in MI rats. In Ang II-stimulated CFs, ellagic acid (60 μmol/L) decreased the protein expression of HDAC1, collagen I, collagen III, MMP-2 and MMP-9, and inhibited cell proliferation and migration. Further, HDAC1 over-expression reversed the inhibitor effects of ellagic acid on proteins expression (collagen I, collagen III, MMP-2 and MMP-9) and proliferation and migration of CFs. The present results suggested that ellagic acid suppressed proliferation and migration of CFs by down-regulating expression of HDAC1.
心肌梗死后心脏成纤维细胞（CFs）可被激活。因此，有必要探索有效药物来抑制心肌梗死后CFs的激活。本研究旨在探讨鞣花酸对CFs的影响及其潜在机制。通过qRT-PCR和蛋白质印迹法检测组蛋白去乙酰化酶（HDACs）和纤维化相关基因的表达。采用Masson三色染色法评估心脏纤维化面积。分别用CCK8试剂盒和Transwell试验检测CFs的增殖和迁移。我们的结果表明，鞣花酸显著降低了心肌梗死大鼠HDAC1的蛋白表达、I型胶原、III型胶原、MMP-2和MMP-9的mRNA表达以及心脏纤维化面积。在血管紧张素II刺激的CFs中，鞣花酸（60 μmol/L）降低了HDAC1、I型胶原、III型胶原、MMP-2和MMP-9的蛋白表达，并抑制了细胞增殖和迁移。此外，HDAC1过表达逆转了鞣花酸对CFs蛋白表达（I型胶原、III型胶原、MMP-2和MMP-9）以及增殖和迁移的抑制作用。目前的结果表明，鞣花酸通过下调HDAC1的表达抑制CFs的增殖和迁移。
