Effects Of APJ Receptor Sntagonist-schizandrin A On Rabbit Platelet Aggregation And Thrombosis Induced By Elabela And Apelin Subtype

Aim: Previous studies in this research group found that endogenous peptides elabela 32,apelin 12,17,36 can promote platelet aggregation and thrombosis through APJ receptor.cell membrane chromatography was used to screen the traditional Chinese medicine monomers that could bind to APJ receptor--Schizandrin A.Combined with pre-laboratory research,explore the effect of Schizandrin A on platelet aggregation ration induced by elabela 32,apelin12,17,36,discuss mitophagy is involved in Schizandrin A inhibiting elabela 32,apelin 12,17,36 induced rabbit platelet aggregation.From APJ receptor perspective,we screen of neotype antiplatelet drug which may provide a new theoretical basis for thrombotic diseases.Methods: 1.The binding capacity of Schizandrin to APJ receptor is analyzed by SYBYLE,2.Platelet aggregation is detected by turbidimetry,3.Thrombosis is observed by rabbit thrombosis detector in vitro,4.Mitochondrial fluorescence probes were used to mark and observe the mitochondria in the platelets,5.The morphology of mitochondrial autophagy in platelets is detected by transmission electron microscopy.Results: 1.Bioinformatics analysis found that Schizandrin A can form 4 binding sites with the three amino acid residues of APJ,2.There is no major effect of Schizandrin A(0.001μmol/L、0.01μmol/L、0.1μmol/L、1.0μmol/L)on rabbit platelet aggregation ration from rabbit rich plasma.Schizandrin A inhibited rabbit platelet aggregation in a dose-dependent manner induced by ADP,3.Schizandrin A(0.001μmol/L、0.01μmol/L、0.1μmol/L、1.0μmol/L)inhibited rabbit platelet aggregation in a dose-dependent manner induced by elabela 32,apelin 12,17,36,4.Schizandrin A(0.001μmol/L、0.01μmol/L、0.1μmol/L、1.0μmol/L)inhibited rabbit thrombosis in a dose-dependent manner induced by elabela 32,apelin 12,17,36,5.A fluorescence probe showed that elabela 32,apelin 12,17,36 reduced the number of mitochondria,which is improved by Schizandrin A,6.The transmission electron microscope demonstrated that elabela 32,apelin 12,17,36 induced rabbit platelet mitophagy,however Schizandrin A inhibited rabbit platelet mitophagy induced by elabela 32,apelin 12,17,36.Conclusion: Schizandrin A inhibits elabela 32,apelin 12,17,36 induced platelet aggregation and in vitro thrombosis through mitophagy.