SIRT1 mediates improvement of cardiac surgery-induced postoperative cognitive dysfunction via the TLR4/NF-κB pathway

Objectives: Clinically, there is no effective therapy for postoperative cognitive dysfunction (POCD). Inflammation after surgery is closely associated with POCD.

Methods: In this study, we explored the role of sirtuin 1 (SIRT1) in POCD. POCD in mice was induced by cardiac surgery. The mRNA and protein levels of related genes were determined by real-time polymerase chain reaction and western blot, respectively. Plasma concentrations of inflammatory factors were measured using an ELISA kit. Novel object and novel location recognition tests were carried out to measure recognition ability. The Morris water maze (MWM) test was performed to measure learning and memory ability.

Results: There was a clear decrease in SIRT1 expression after POCD. The SIRT1 activator SRT1720 promoted recognition, learning, and memory ability of mice with POCD. Moreover, SRT1720 treatment greatly inhibited plasma inflammatory cytokine levels and TLR4 and P65 protein expression in the hippocampus of POCD mice. The effect of SRT1720 on POCD was in a TLR4-dependent manner.

Conclusions: SIRT1 mediates the improvement of cardiac surgery-induced postoperative cognitive dysfunction via the TLR4/NF-κB pathway.