Effect of human umbilical cord mesenchymal stem cell exosomes on myocardial fibrosis in rats with Adriamycin-induced dilated cardiomyopathy / 中华实用儿科临床杂志

ABSTRACT

Objective:To evaluate the effects of human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-ex) injection on cardiac function and myocardial fibrosis in dilated cardiomyopathy (DCM) rats induced by Adriamycin(ADR).Methods:One hundred male SD rats were randomly divided into the normal group (20 rats) and the DCM group (80 rats). The rats in DCM group were treated with ADR by intravenous injection to induce DCM.DCM rats were randomly divided equally into DCM group, low-dose group, medium-dose group and high-dose group which were received intravenous injection 1 mL/kg Dulbecco′s modified eagle medium(DMEM), 20 μg/kg, 100 μg/kg and 250 μg/kg exosomes.After modeling, 10 rats in normal group and 30 rats in DCM group were randomly selected to receive echocardiography to evaluate the cardiac function.After exosomes treatment, 10 rats were randomly selected form each group for echocardiography to evaluate the cardiac function.The morphological changes in myocardial cells were observed by using Masson staining in each group; Western blot detection between groups of rats was used to analyze the expression of myocardial collagen Ⅰ type(COLⅠ), Smad2 and alpha smooth muscle actin (α-SMA).Results:Left ventricular ejection fraction(LVEF) and left ventricular fraction shortening (LVFS)in the DCM group [(64.30±3.51)% and (38.70±2.85)%] were significantly lower than those of the normal group [(78.80±1.52)% and (50.60±1.50)%], and the differences were statistically significant ( t=20.518, 22.311, all P<0.01). The left ventricular end-diastolic diameter(LVEDD) and left ventricular end-systolic diameter (LVESD) [(4.62±0.13) mm and (3.40±0.12) mm] of the DCM group were significantly higher than those of the normal group[(3.29±0.24) mm and (3.16±0.33) mm], and the differences were statistically significant( t=2.854, 3.800, all P<0.01). After exosomes treatment, LVEF[(84.3±2.6)% and (83.4±3.2)%] in the medium-dose and high-dose groups were significantly higher than that in the DCM group [(79.2±2.4)%], and the diffe-rences were statistically significant(all P<0.01). Masson staining found that collagen fibers were less in exosomes treating group than those in the DCM group; Western blot test showed that high-dose exosomes can reduce the expression of α-SMA and Smad2, high-dose and low-dose exosomes can both significantly reduce the expression of COLⅠ. Conclusions:It suggests that exosomes intravenous injection from hUCMSCs-ex can significantly improve myocardial fibrosis in DCM rats induced by ADR and cardiac function.