Syringin improves myocardial mitochondrial dynamics and alleviates oxidative stress injury in septic mice by activating SIRT3

To investigate the protective effects of syringin against septic myocardial injury and explore the underlying mechanisms.

Thirty C57 mice were randomly assigned to receive sham operation with or without subsequent syringin treatment or sepsis modeling by cecal ligation and puncture (CLP) followed by intraperitoneal injection of saline, syringin, or both syringin and 3-TYP (an SIRT3 inhibitor). Cardiac function and myocardial injury of the mice were assessed with echocardiography and HE staining, and serum cTnT, LDH, MDA, SOD, and GSH-Px levels were detected using ELISA. ROS production and expressions of p-DRP1, MFN1, and NOX4 were detected with immunohistochemistry and immunofluorescence staining, and the expressions of the SIRT3/NOX2/p-DRP1 pathway proteins were determined with Western blotting. In primary culture of neonatal mouse cardiomyocytes (NMCMs) treated with lipopolysaccharide (LPS), the effects of syringin, syringin combined with 3-TYP, and honokiol on mitochondrial membrane potential and expression of the SIRT3/NOX2/p-DRP1 pathway were analyzed by immunofluorescence staining and Western blotting.

CLP mice exhibited significant impairment of cardiac function, obvious myocardial injury, elevated serum cTnT and LDH levels, and increased expression of oxidative stress- and mitochondrial injury-related proteins. Syringin treatment significantly improved myocardial structure and cardiac function, attenuated oxidative stress, and reduced mitochondrial damage in the CLP mice. Treatment with 3-TYP significantly abolished the protective effects of syringin and resulted in increased MDA and cTnT levels, decreased SOD activity, elevated ROS production, and increased expressions of oxidative stress and mitochondrial injury markers. In NMCMs, LPS stimulation obviously reduced mitochondrial membrane potential, increased AC-SOD2, NOX2, and p-DRP1 expressions, and decreased MFN1 levels. Syringin significantly alleviated LPS-induced oxidative stress and mitochondrial dysfunction, and these effects were abolished by 3-TYP treatment or SIRT3 silencing.

Syringin attenuates sepsis-induced myocardial injury by activating SIRT3 to improve cardiac function, suppress oxidative stress, and alleviate mitochondrial damage.