Exosomes derived from Danshen decoction-pretreated bone marrow mesenchymal stem cells alleviate myocardial infarction via anti-apoptosis and up-regulation of autophagy

Abstract

Cardiomyocyte loss and myocardial fibrosis are major determinants of myocardial infarction (MI) pathological changes. Mesenchymal stem cell (MSC)-derived exosomes (exos) and Danshen decoction (DSY) have been demonstrated to mediate cardiac repair following MI. BM-MSCs exos or BM-MSCsDSY exos were intramuscularly injected into post-MI rats. On the 7th, 14th and 28th days, serum CK, LDH, α-HBDH, ALT, and AST were measured and electrocardiogram changes were monitored to identify cardiac function; Triphenyltetrazolium chloride staining, Hematein&Eosin staining, Masson trichrome staining and Transmission Electron Microscope were adopted to analyze infarct area, cardiac morphology, histopathology, and fibrosis and cardiomyocyte ultrastructure; TUNEL assay, real-time PCR and western blot were performed to detect cardiomyocyte apoptosis and autophagy. As a result, BMMSCsDSY exos are superior to BM‐MSCs‐exos in improvement of cardiac function, morphology, histopathology and cardiomyocyte ultrastructure, as well as in reduction of infarction area and cardiac fibrosis by inhibiting apoptosis and promoting autophagy of cardiomyocytes.