Crocin alleviates pressure overload-induced cardiac hypertrophy by upregulating Nrf2/HO-1 signaling
Objective To investigate the effect of crocin(Cro)on pressure overload-induced cardiac hypertrophy and explore its underlying mechanism.Methods C57BL/6J mice were randomly divided into four groups:sham group,transverse aortic constriction(TAC)group,Cro+TAC group and Cro+ML385(a Nrf2 inhibitor)+TAC group.Cardiac hypertrophy model was established by transverse aortic constriction.Mice in sham group and TAC group were given saline by gavage,while mice in Cro+TAC group were given Cro(40 mg/kg)by gavage after transverse aortic constriction surgery,and mice in Cro+ML385+TAC group were simultaneously given Cro(40 mg/kg)by gavage and an intraperitoneal injection of ML385(30 mg/kg)for four weeks.Cardiac functions including left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS)and end-diastolic ventricular septal thickness(I VST)were measured.The ratio of heart weight to body weight(HW/BW)was calculated.The mRNA levels of ANP and BNP were detected by reverse transcription polymerase chain reaction(RT-PCR).The myocardial cross-sectional area was observed by wheat germ agglutinin(WGA)staining.Myocardial fibrosis was assessed by Masson staining.MDA content and SOD activity in myocardial tissue were detected by ELISA.The protein levels of SOD2,gp91phox,Nrf2 and HO-1 were determined by Western blot.Results Compared with sham group,LVEF and LVFS were decreased significantly in TAC group,and IVST,HW/BW ratio,the mRNA levels of ANP and BNP,the cell cross-sectional area,the fibrosis and MDA content were increased(P＜0.05).Compared with sham group,SOD activity and the protein levels of SOD2,Nrf2 and HO-1 were decreased in TAC group(P＜0.05),while gp91phox protein level was elevated(P＜0.01).Compared with TAC group,LVEF and LVFS were increased significantly in Cro+TAC group,meanwhile,IVST,HW/BW ratio,the mRNA levels of ANP and BNP,the cell cross-sectional area,the fibrosis and MDA content were decreased in Cro+TAC group(P＜0.05).Compared with TAC group,SOD activity was increased in Cro+TAC group(P＜0.05)and the protein levels of SOD2,Nrf2 and HO-1 were increased(P＜0.01),while gp91phox protein level was inhibited(P＜0.01).Compared with Cro+TAC group,LVEF and LVFS were decreased significantly in Cro+ML385+TAC group(P＜0.05),meanwhile,IVST,HW/BW ratio,the mRNA levels of ANP and BNP,the cell cross-sectional area,the fibrosis and MDA content were increased in Cro+ML385+TAC group(P＜0.05).In addition,compared with Cro+TAC group,SOD activity was decreased in Cro+ML385+TAC group(P＜0.05),the protein levels of SOD2,Nrf2 and HO-1 were decreased(P＜0.01),while gp91phox protein level was elevated(P＜0.01).Conclusion Crocin can inhibit the fibrosis and improve the pressure overload-induced cardiac hypertrophy by upregulating Nrf2/HO-1 signaling.
万方数据
维普
