Abstract: To investigate the effects of propofol (Pro) on hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes via regulation of the silent information regulator 1(SIRT1)/p53 signaling pathway-mediated ferroptosis, an in vitro H9C2 cell H/R model was established. Cells were divided into the following groups: Control group, H/R group, H/R+Pro group, H/R+Pro+erastin group, H/R+Pro+si-NC group, and H/R+Pro+si-SIRT1 group. The cytotoxic effect of Pro on H9C2 cells was assessed using the cell counting kit-8 (CCK-8) assay. Intracellular reactive oxygen species (ROS) levels were measured using the 2', 7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe. Mitochondrial ultrastructure was examined by transmission electron microscopy (TEM). Oxidative stress markers were quantified using corresponding assay kits. Expression levels of ferroptosis-related proteins were detected by Western blot. Results demonstrated that compared to the Control group, the H/R group exhibited significantly reduced cell viability, elevated levels of ROS and malondialdehyde (MDA), decreased levels of catalase (CAT) and superoxide dismutase (SOD), nuclear membrane rupture, increased mitochondrial membrane density, loss of mitochondrial cristae, swelling and rupture of mitochondria, increased Fe2+ content and lactate dehydrogenase (LDH) activity, elevated levels of acyl-CoA synthetase long-chain family member 4 (ACSL4) and p53, and reduced levels of glutathione peroxidase 4 (GPX4) and SIRT1 (P<0.05). Pro treatment significantly ameliorated H/R injury, increasing cell viability and elevating SOD, CAT, GPX4, and SIRT1 levels, while reducing Fe2+ content, ROS, MDA, ACSL4, and p53 levels, and restoring mitochondrial structure (P<0.05). Erastin partially reversed the protective effects of Pro (P<0.05). Conversely, si-SIRT1 completely abolished the effects of Pro, resulting in decreased GPX4 levels and increased Fe2+ content and ACSL4 levels (P<0.05). This study revealed that Propofol likely protects cardiomyocytes against H/R injury by activating the SIRT1/p53 pathway to inhibit ferroptosis. This finding provides crucial mechanistic insight into Propofol-mediated cardioprotection and suggests a potential novel strategy for the prevention and treatment of myocardial ischemia-reperfusion injury.
Key words: propofol; silent information regulator 1/p53 signaling pathway; ferroptosis; cardiomyocytes; hypoxia/reoxygenation injury
（Acta Laser Biology Sinica, 2025, 34(6): 561-568）