Salvianolic Acid Salts Mediate the Cell Pyroptosis Pathway through the MAVS-NLRP3-GSDMD Signaling Pathway to Counteract Myocardial Toxicity
LIU Jiang
LI Jian
Abstract：Objective:To study the protective effect of salvianolic acid salts on doxorubicin-induced myocardial toxicity and their effects on the mitochondrial antiviral signaling protein(MAVS)-NOD-like receptor pyrin domain-containing protein 3(NLRP3)-gasdermin D(GSDMD)signaling pathway in cell pyroptosis.Methods:Sixty rats were randomly divided into the control group,model group,low-dose group,medium-dose group,and high-dose group.A myocardial injury model was established by intraperitoneal injection of doxorubicin,while the low-,medium-,and high-dose groups were intervened by intraperitoneal injection of 10,20,and 40 mg/kg salvianolic acid salts,respectively.After 4 weeks,cardiac function indicators were detected by ultrasound,haematoxylin-eosin staining was performed for pathological tissue observation,and the expression levels of antioxidant indicators,as well as the mRNA and protein levels of the MAVS-NLRP3-GSDMD signaling pathway in myocardial tissue,were measured.Results:Salvianolic acid sodium intervention can significantly increase left ventricular ejection fraction,reduce left ventricular end-diastolic and end-systolic diameters,reverse the increase in left ventricular shortening rate,increase superoxide dismutase(SOD)in myocardial tissue,decrease catalase(CAT),and inhibit the elevation of malondialdehyde(MDA),with all significant differences(P＜0.05).In the model group,the myocardial structure of rats was disordered,the arrangement of myocardial cells was unorganized,a large number of cells swelled and necrosis,the inflammatory infiltration was severe,and vacuoles presented.The intervention of salvianolic acid salts could significantly improve the arrangement of myocardial cells in rats,reduce cell swelling and necrosis,alleviate inflammatory cell infiltration,and the improvement effect was enhanced with the increase of dose.The mRNA and protein expressions of GSDMD,Caspase-1,NLRP3,MAVS,interleukin(IL)-1β,and IL-18 in the myocardium of rats in the model group significantly increased(P＜0.05),and the intervention of salvianolic acid salts down-regulated the mRNA and protein expressions of the above pathways.Conclusion:Salvianolic acid salts can alleviate doxorubicin-induced myocardial toxicity,downregulate the MAVS-NLRP3-GSDMD signaling pathway,alleviate myocardial cell pyroptosis,and exerts cardioprotective effects.
Keywords：cell pyroptosismyocardial toxicitysalvianolic acid saltsmitochondrial antiviral signaling proteinNOD-like receptor pyrin domain-containing protein 3Caspase-1experimental study
Publication Date：2025-10-25
Online Publishing Date：2025-11-03(First online date of this platform, not the publication date of the document)
Pages：6( 3074-3079 )