Salvianolic acid B promotes mitochondrial homeostasis and improves cardiac function in mice with ischemia-reperfusion injury by inhibiting Sirt1 protein degradation
LI Simeng
CHEN Jianning
SHEN Siman
LIU Wanglong
YU Lili
ZHANG Liangqing
Abstract：Objective To investigate the molecular mechanism by which salvianolic acid B(Sal-B)modulates mitochondrial functional homeostasis and alleviates myocardial ischemia-reperfusion(I/R)injury in mice.Methods Mouse cardiomyocyte HL-1 cells were pretreated with 5 μmol/L Sal-B with or without sh-Sirt1 transfection before exposure to hypoxia-reoxygenation(HR),and the changes in ATP production,mitochondrial superoxide activity,substrate oxidation level were evaluated.In the animal experiment,36 C57BL/6J mice were randomized into 3 groups(n=12)for sham operation or ligation of the left anterior coronary artery to induce myocardial I/R injury with or without intravenous injection of Sal-B+I/R(50 mg/kg).In the rescue experiment,60 adult C57BL/6J mice were randomized into 5 groups(n=12):sham-operated group,myocardial I/R group,Sal-B+I/R group,I/R+Sal-B+Sirt1fl/fl group,and I/R+Sal-B+cKO-Sirt1 group.Myocardial injury was evaluated with HE staining,and cardiac function was assessed by measurement of the ejection fraction and fractional shortening using echocardiography.Results In HL-1 cells with HR injury,Sal-B pretreatment significantly increased cellular ATP production,reduced mitochondrial superoxide anion levels,and enhanced oxygen consumption level.In the mouse models of myocardial I/R injury,Sal-B pretreatment markedly ameliorated I/R-induced structural disarray of the cardiac myocytes and improved cardiac ejection.Cycloheximide chase with Western blotting and ubiquitination assays after Sirt1-IP showed that Sal-B significantly inhibited Sirt1 degradation in HL-1 cells.Sirt1 knock-down reversed Sal-B-induced increases in ATP production,reduction in superoxide,and elevation of OCR in HL-1 cells.Cardiomyocyte-specific Sirt1 knockout obviously reversed Sal-B-mediated improvement in cardiac ejection function and myocardial structure damage in mice with myocardial I/R injury.Conclusion Sal-B promotes mitochondrial functional homeostasis in cardiomyocytes with HR injury and improves cardiac function in mice after myocardial I/R by inhibiting Sirt1 protein degradation.
Keywords：salvianolic acid BSirt1myocardial ischemia-reperfusion injuryheartmitochondrial homeostasis
Publication Date：2025-10-20
Online Publishing Date：2025-11-03(First online date of this platform, not the publication date of the document)
Pages：9( 2062-2070 )