Resveratrol ameliorates neuronal apoptosis and cognitive impairment by activating the SIRT1/RhoA pathway in rats after anesthesia with sevoflurane

Studies have shown that long-term exposure to sevoflurane (SEV) may cause post-operative cognitive dysfunction. This study aimed to investigate the effects of resveratrol (RES) treatment on the changes in the cognitive function of rats after prolonged anesthesia with SEV. Seventy-six adult male rats were used in this study. The SEV model was established under continuous anesthesia for 6 hours. Rats were randomly classified into four groups as follows: Control, SEV+vehicle, SEV+pre-RES (RES was administered 24 hours before establishing the SEV model), and SEV+post-RES (RES was administered 1 hour after establishing the SEV model) groups. Neurobehavioral outcomes and the potential mechanism underlying RES-mediated neuroprotection through the silent information regulator 1 (SIRT1)/RhoA signaling pathway were evaluated. The water maze test showed that long-term exposure to SEV may lead to loss of learning and memory ability in rats (p < 0.05). Compared with the SEV+vehicle group, the RES treatment groups showed significantly improved neurobehavioral scores (p < 0.05). In addition, the SEV+pre-RES group had a better outcome than the SEV+vehicle group on days 1 or 2 (p < 0.05), unlike the SEV+post-RES group (p > 0.05). Western blotting showed that SIRT1, RhoA, and cleaved Caspase-3 (CC3) expression significantly increased in the SEV+vehicle group (p < 0.05), while Bcl2 expression decreased (p < 0.05). RES treatment further upregulated SIRT1 and Bcl2 expression and downregulated the expression of RhoA and CC3 (p < 0.05). In conclusion, RES treatment improved cognitive dysfunction by reducing neuronal apoptosis in adult rats exposed to SEV. RES partly exerted a neuroprotective effect through the activation of the SIRT1/RhoA signaling pathway.