Yixin Formula Alleviates Myocardial Ischemia-reperfusion Injury in Rats via Modulating SIRT1/Nrf2/HO-1 Signaling Pathway
Objective To explore the role and its mechanism of Yixin Formula(YXF)on myocardial ischemia-reperfusion injury(MIRI)in rats.Methods Totally 75 Wistar rats were divided into five groups randomly:Sham,IR,YXF+IR,YXF+IR+SIRT1-inhibitor(EX527),and YXF+IR+SIRT1-agonist(SRT1720)groups,15 in each group.Cardiac function was measured by echocardiography,immunofluorescence was performed to detect apoptosis and reactive oxygen species(ROS)level in heart tissues after 7 days of reperfusion.The level of serum myocardial enzymes was detected by ELISA.Subsequently,the expression of related proteins was detected by Western Blot.Results Compared with the Sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)of the rats in the IR group were decreased,the apoptosis rate,ROS,creatine kinase(CK),lactate dehydrogenase(LDH),malondialdehyde(MDA),hydrogen peroxide(H2O2),and succinate dehydrogenase(SDH)were significantly increased in the IR group,while superoxide dismutase(SOD)level was decreased.The protein expression of silent information regulatory factor 1(SIRT1),nuclearfactor erythroidderived 2-like 2(Nrf2),heme oxygenase-1(HO-1),and B-cell lymphoma-2(Bcl-2)were decreased,while Bcl2-associated X(Bax)and cysteinyl aspartate specific proteinase 3(Caspase 3)were increased in the IR group,the differences were statistically significant(P＜0.01,P＜0.05).Compared with IR group,LVEF and LVFS increased,apoptotic index and ROS decreased,the level of CK,LDH,MDA,H2O2 and SDH decreased,and the SOD level increased,the protein expression of SIRT1,Nrf2,HO-1 and Bcl-2 was increased,while Bax and Caspase 3 were decreased in YXF+IR and YXF+IR+SRT1720 groups,the differences were statistically significant(P＜0.01,P＜0.05).Compared with YXF+IR group,CK,LDH,MDA,H2O2 and SDH levels increased,while SOD level decreased,the protein expressions of SIRT1,Nrf2,HO-1 and Bcl-2 decreased,while Bax and Caspase 3 expression increased in YXF+IR+EX527 group,the differences were statistically significant(P＜0.01,P＜0.05).Conclusion YXF can improve cardiac function and reduce oxidative stress injury after myocardial ischemia/reperfusion in MIRI rats by upregulating SIRT1/Nrf2/HO-1 signaling pathway.
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