Knockdown of TNFAIP1 mitigates sevoflurane-induced cognitive dysfunction by activating CREB/Nrf2 pathway

Abstract

Purpose: To investigate the role of tumor necrosis factor-induced protein 1 (TNFAIP1) and cAMPresponsive element binding protein (CREB)/nuclear factor-erythroid factor 2-related factor 2 (Nrf2) pathway in sevoflurane (SEV)-induced cognitive dysfunction. Methods: A SEV-induced cognitive dysfunction rat model was developed. Bcl-2, Bax, heme oxygenase-1, Nrf2, p-CREB, and CREB protein levels in rat hippocampal tissue were assessed by western blot. Learning and long-term memory were evaluated using Morris water maze test. Glutathione peroxidase, malondialdehyde, and superoxide dismutase levels in hippocampal tissue were measured by enzyme-linked immunosorbent assay (ELISA). The 2,7-dichlorodihydro-fluorescein diacetate fluorescent assay was used to measure reactive oxygen species, while TUNEL staining was used to assess neuronal cell apoptosis. Results: Knockdown of TNFAIP1 attenuated SEV-induced learning and long-term memory dysfunction (p < 0.005), oxidative stress (p < 0.005), apoptosis (p < 0.005), and inhibition of the CREB/Nrf2 signaling pathway. Conclusion: This study demonstrates that knockdown of TNFAIP1 alleviates SEV-induced cognitive dysfunction by reversing inhibition of the CREB/Nrf2 signaling pathway. Keywords: TNFAIP1; Postoperative cognitive dysfunction; Sevoflurane; cAMP-responsive element binding protein (CREB); Nuclear factor-erythroid factor 2-related factor 2 (Nrf2)