RESUMEN
Objective To investigate the protective effect of hyperoside(Hyp)on transverse aortic constriction-in-duced cardiac hypertrophy and its possible mechanism.Methods Forty 8-week-old male C57BL/6J mice were randomly divided into four groups:Sham group,TAC group,Hyp+TAC group and Hyp+ML385+TAC group.Four weeks after operation,cardiac function including left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS)and left ventricular end-diastolic posterior wall thickness(LVPWd)were measured with echocardiography.HE staining was used to evaluate the myocyte cross-sectional area.Masson staining was used to determine myocardial fibrosis.The ratio of heart weight/body weight was calculated.DHE staining was used to assess reactive oxygen species(ROS)production.The mRNA levels of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and β-myosin heavy chain(β-MHC)were detected by qRT-PCR.The protein levels of NF-E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),superoxide dismutase2(SOD2)and NAD-PH-Oxidase 2(gp91phox)were detected by Western blot.Differences among groups were compared by one-way a-nalysis of variance,and LSD-t test was used for comparison between the two groups.Results Compared with the Sham group,the values of LVEF and LVFS in the TAC group decreased(P＜0.01).The value of LVPWd,the cross-sectional area,fibrosis and the ratio of HW/BW increased(P＜0.01).The mRNA levels of ANP,BNP andβ-MHC were upregulated(P＜0.01).The ROS production and gp91phox protein level were elevated in the TAC group(P＜0.01),while the protein levels of Nrf2,HO-1 and SOD2 decreased(P＜0.01).Compared with the TAC group,the values of LVEF and LVFS in the Hyp+TAC group increased(P＜0.01).The value of LVPWd,the cross-sectional area,fibrosis and the ratio of HW/BW decreased(P＜0.01).The mRNA levels of ANP,BNP and β-MHC were downregulated(P＜0.01).The ROS production and gp91 phox protein levels were reduced in the Hyp+TAC group(P＜0.01),while the protein levels of Nrf2,HO-1 and SOD2 increased(P＜0.01).However,ML385 could partially reverse the protective effects of Hyp on TAC-induced cardiac hypertrophy.Conclusion Hyp alleviates pressure overload-induced cardiac hypertrophy by inhibiting oxidative stress and fibrosis,and its mechanism may be related to Nrf2/HO-1 signaling.