Effect of 2-methoxyestradiol nanoparticles combined with propofol on hippocampal nerve cells and metabolism after cerebral ischemia-reperfusion

Abstract

Short-term or permanent reduction in cerebral blood flow can lead to cerebral ischemia, and if it persists, it can lead to necrosis and cell death. Reperfusion is restoration of blood supply, but it may further aggravate the damage of ischemic brain tissue. Propofol has characteristics such as rapid recovery, continuous infusion, and no accumulation. 2-Methoxyestradiol (2ME2) is a HIF-1-α inhibitor and reduces cell apoptosis. The brain ischemia-reperfusion hippocampal nerve cell model was in this study prepared in vitro. Samples were randomly assigned into control group (control), cerebral ischemia-reperfusion (CIR) group, propofol group (Propofol), 2ME2 nanoparticle group (2ME2-NPs), and combination group (Propofol+2ME2-NPs). The changes of cell proliferation and apoptosis activities were analyzed in each group, which included changes of Survivin expression, changes of intracellular Adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, and ATP, respectively) changes of malondialdehyde (MDA) and superoxide dismutase (SOD) Analysis also included secretion of IL-6 and TNF-α, and detection of HIF-1α and NF-κB expression. Results revealed that, CIR hippocampal nerve cell proliferation decreased, apoptosis activity increased, while Survivin expression increased. Moreover, ATP, ADP and AMP contents decreased, while secretion of inflammatory factors IL-6 and TNF-α increased, MDA increased, and SOD decreased. HIF-1α and NF-κB expressions increased. Propofol and 2ME2 nanoparticles promoted hippocampal neurons proliferation after CIR brain injury, inhibit the apoptotic activity, and reduce the expression of apoptotic protein Survivin. ATP, ADP and AMP content increased, IL-6 and TNF-α decreased, MDA decreased, SOD activity increased, HIF-1α and NF-κB decreased. The and combined group had a more significant effect. 2ME2 nanoparticles combined with propofol can inhibit HIF-1α and secretion of inflammatory factors by regulating oxidative stress and NF-κB signaling pathways, promoting the proliferation of hippocampal neurons, inhibiting apoptosis, and restoring cell energy and helping to restore nerve cell function.