Effects of edaravone on the expression of TGF-β1 and myocardialfibrosis in rats / 天津医药

ABSTRACT

Objective To investigate the effects of edaravone on myocardial fibrosis induced by isoproterenol (ISO) in rats, and to discuss the correlation between the level of transforming growth factor-β1 (TGF-β1) and the myocardial fibrosis. Methods Forty male SD rats were randomly divided into five groups, namely control group, model group and edaravone groups (low, medium and high doses). Isoproterenol was used to establish the rat model of myocardial fibrosis. Edaravone groups were given edaravone [3, 5 and 10 mg/(kg · d)] to intervene for 14 days. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were examined after 15-d treatment. The left ventricular mass index (LVMI) and collagen volume fraction (CVF) were examined. The expression of TGF-β1 was detected by Western blot assay and immuno-fluorescence method. Results The content of MDA and LVMI were significantly higher in model group than those of the control group (P<0.01),whereas the content of SOD was significantly lower in model group than that of the control group (P<0.01). Compared with model group, the expression level of MDA decreased with the increased intervention dose of edara-vone (P<0.05), while SOD expression level increased (P<0.05). There was no significant difference in the level of SOD be-tween middle dose edaravone group and the control group. LVMI was decreased with the increased doses of edaravone ( P<0.01). There was no significant difference in LVMI between the high dose of edaravone group and the control group. Com-pared with the control group, the expression level of TGF-β1 was significantly increased in model group (P<0.01). The ex-pression level of TGF-β1 was reduced with the increased doses of edaravone. CVF was significantly increased in model group compared with that of control group (P<0.001). CVF decreased with the increased doses of edaravone in medium and high doses of edaravone groups, but they were higher than that of control group (P<0.01). TGF-β1 was positively correlated with MDA, LVMI and CVF (r=0.931, 0.879 and 0.930, P<0.001). SOD was negatively correlated with TGF-β1 (r=-0.892, P<0.001). Conclusion Edaravone can relieve myocardial fibrosis by inhibiting oxidative stress and TGF-β1 in rats.