Objective:To explore the effects and possible mechanism of Tongmai Yangxin Pills(TMYXP)on myocardial ischemia-reperfusion injury(MIRI)in rats.Methods:SD rats were randomly divided into sham-operation group,model group,TMYXP low-dose group,TMYXP medium-dose group,TMYXP high-dose group and inhibitor group,18 rats in each group.The sham operation group and model group were given 0.5％carboxymethylcellulose sodium by gavage;the TMYXP low,medium,and high dose groups were given 1.0,2.0 and 4.0 g·kg-1·d-1 of TMYXP by gavage,respectively;and the inhibitor group was given 4.0 g·kg-1·d-1 of TMYXP by gavage and intraperitoneal injection of EX-527(5 mg·kg-1·d-1).The rat MIRI model was constructed by ligating the anterior descending branch of the coronary artery for 30 min and reperfusion for 2 h after the last administration of the drug for 7 days.The operation of the sham-operated group was the same as that of the model group,but the anterior descending branch was threaded only and not ligated.The area of myocardial infarction in rats was evaluated with TTC staining method;apoptosis of cardiomyocytes was observed with TUNEL staining;and the kit detected the lactate dehydrogenase(LDH)and creatine kinase isoenzyme(CK-MB)in the serum,and superoxide dismutase(SOD),malondialdehyde(MDA)and catalase(CAT)levels in myocardial tissues;silent information regulator 1(SIRT1)deacetylase fluorescence assay kit measured SIRT1 activity;Western Bolt was detected SIRT1,acetylated forkhead-like transcription factor 1(Acetyl-FOXO1),manganese superoxide dismutase(MnSOD),B-cell lymphoma 2(BCL-2),BCL-2-associated X(Bax),and Cleaved-Caspase-3 protein expression levels in the S1RT1/FOXO1 signaling pathway.Results:Compared with the sham-operated group,myocardial infarction area,LDH,CK-MB,and MDA levels,and protein expression of Acetyl-FOXO1,Bax,and Cleaved-Caspase-3 were significantly higher in the model group of rats(P＜0.05);a large number of TUNEL-positive cells were present in myocardial tissues;and SOD and CAT levels,SIRT1 activity,SIRT1,MnSOD,and BCL-2 protein expression were all significantly reduced(P＜0.05).Compared with the model group,myocardial infarction area,levels of LDH,CK-MB,and MDA,and protein expression of Acetyl-FOXOI,Bax,and Cleaved-Caspase3 were decreased in rats in the low,medium,and high dose groups of TMYXP(P＜0.05);the number of TUNEL-positive cells was reduced;and SOD and CAT levels,SIRT1 activity,SIRT1,MnSOD,and BCL-2 protein expression were all significantly elevated(P＜0.05).Compared with the TMYXP high-dose group,myocardial infarction area,levels of LDH,CK-MB,and MDA,and protein expression of Acetyl-FOXO1,Bax,and Cleaved-Caspase-3 were elevated in the inhibitor group(P＜0.05);the number of TUNEL-positive cells was increased;and SOD and CAT levels,SIRT1 activity,SIRT1,MnSOD,and BCL-2 protein expression were all decreased(P＜0.05).Conclusion:TMYXP pretreatment can improve MIRI,and its mechanism of action may be related to its activation of the SIRT1/FOXO1 signaling pathway to exert anti-oxidative stress and anti-apoptotic effects.
Myocardial ischemia-reperfusion injury(MIRI)Tongmai Yangxin PillsOxidative stressApoptosisSIRT1/FOXO1 signaling pathwayTraditional Chinese medicineMechanism
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