Propofol and Salvianolic Acid a Synergistically Attenuate LPS-Induced Myocardial Pyroptosis in Diabetic Mice via the SIRT1/HMGB1 Pathway.

BACKGROUND

We investigated whether propofol (PPF) combined with salvianolic acid A (SAA) confers synergistic cardioprotection in diabetic sepsis.

METHODS

Diabetic-septic mice and high-glucose/LPS-treated cardiomyocytes were treated with PPF and SAA. Cardiac function, reactive oxygen species (ROS), inflammation, and the SIRT1/HMGB1 pathway were assessed.

RESULTS

PPF combined with SAA synergistically attenuated cardiac inflammation, pyroptosis, and dysfunction, accompanied by SIRT1 upregulation and HMGB1 downregulation. Notably, low-dose coadministration of PPF (12.5 µM) and SAA (12.5 µM) achieved protection comparable to high-dose PPF (25 µM), significantly reducing ROS and pyroptosis markers. These protective effects were reversed by SIRT1 inhibition or silencing but enhanced by HMGB1 inhibition.

CONCLUSION

PPF and SAA synergistically inhibit LPS-induced myocardial pyroptosis under hyperglycemia by activating the SIRT1/HMGB1 pathway. This combination offers a potential strategy to enhance cardioprotection while minimizing anesthetic dosage.