Effects of Aucubin on Nrf2-mediated Ferroptosis Pathway in Rats with Coronary Heart Disease
Objective:To explore the therapeutic effect of aucubin(AU)on rats with coronary heart disease(CHD)and its effect on the ferroptosis pathway mediated by nuclear factor erythroid 2-related factor 2(Nrf2).Methods:Rats were divided into NC group,CHD group,L-AU group,M-AU group,H-AU group and ML385 group(n=12).The NC group was control rats fed with normal diet,and the other groups were rats with coronary heart disease induced by high-fat diet combined with intraperitoneal injection of pituitaryin.Rats in the NC group and CHD group were orally administered 0.3％sodium carboxymethylcellulose(CMC),and rats in the L-AU group,M-AU group,and H-AU group were orally administered 20,40,and 80 mg/kg/d of aucubin.Rats in H-AU group were orally adminis-tered 80 mg/kg/d aucubin and intraperitoneally injected with 30 mg/kg/d Nrf2 inhibitor ML385.Administration was given for a total of 4 weeks.The cardiac function indexes[ejection fraction(EF)and fractional shortening(FS)],serum indexes[creatine kinase isoenzyme MB(CK-MB),lactate dehydrogenase(LDH),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)and free fatty acids(FFA)],myocardial tissue oxidative stress indicators[glutathione(GSH)and malondialdehyde(MDA)]and Fe2+content in myocardial tissue of rats in each group were measured respectively.Myocardial mor-phology was observed by hematoxylin-eosin(HE)staining.The protein expression levels of Nrf2,Kelch-like ECH-associated protein 1(Keapl),heme oxygenase-1(HO-1),NADPH:quinone oxidoreductase-1(NQO-1),glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and membrane iron transporter 1(FPN1)in myocardial tissue were detected by Western blot.Results:Compared with NC group,EF and FS decreased,CK-MB and LDH levels increased,myocardial injury appeared,TC,TG,LDL-C,FFA and MDA levels in-creased,HDL-C and GSH level decreased,Nrf2,HO-1,NQO-1,GPX4,FTH1 and FPN1 protein expression decreased,Keap1 protein ex-pression increased,Fe2+content increased in CHD group(P＜0.05).Compared with CHD group,EF and FS increased,CK-MB and LDH levels decreased,myocardial morphology was significantly improved,TC,TG,LDL-C,FFA and MDA levels decreased,HDL-C and GSH level increased,Nrf2,HO-1,NQO-1,GPX4,FTH1 and FPN1 protein expression increased,Keap1 protein expression decreased and Fe2+content decreased in L-AU group,M-AU group and H-AU group(P＜0.05).Compared with H-AU group,EF and FS decreased,CK-MB and LDH increased,myocardial injury aggravated,TC,TG,LDL-C,FFA and MDA increased,HDL-C and GSH decreased,Nrf2,HO-1,NQO-1,GPX4,FTH1 and FPN1 protein expression decreased,Keap1 protein expression increased,Fe2+content increased in ML385 group(P＜0.05).Conclusion:Auucrin shows good anti-coronary heart disease effect,and its mechanism is related to inhibiting the Nrf2-mediated ferroptosis pathway.
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