Protective effect of trimetazidine in radiation-induced cardiac fibrosis in mice

Abstract

Radiation-induced heart damage is a serious side effect caused by radiotherapy, especially during the treatment of cancer near the chest. Trimetazidine is effective at reducing inflammation in the heart, but how it affects radiationinduced cardiac fibrosis (RICF) is unknown. To investigate the potential effect and molecular mechanism, we designed this project with a C57BL6malemouse model supposing trimetazidine could inhibit RICF inmice. During the experiment, mice were randomly divided into six groups including a control group (Con), radiation-damaged model group (Mod) and four experimental groups receiving low-dose (10mg/kg/day) or high-dose (20mg/kg/day) trimetazidine before or after radiation treatment. Apart fromthe control group, all mice chests were exposed to 6MV X-rays at a single dose of 20Gy to induce RICF, and tissue analysis was done at8weeks after irradiation.Fibroblast or interstitial tissues and cardiac fibrosis-like characteristics were determined using haematoxylin and eosin andMasson staining, which can be used to assess myocardial fibrosis. Immunohistochemical analysis and RT-PCR were used to determine gene expression and study the molecular mechanism. As a result, this study suggests that trimetazidine inhibits RICF by reducing gene expression related tomyocyte apoptosis and fibrosis formation, i.e. connective tissue growth factor (CTGF), transforming growth factor (TGF)-β1, smad2 and smad3. In conclusion, by regulating the CTGF/TGF-β1/Smad pathway, trimetazidine could be a prospective drug for clinical treatment of RICF.