Based on the AMPK/PGC-1α/SIRT3 signaling pathway, the effect and mechanism of remimazolam in improving neurocognitive impairment after tibial fracture in elderly mice was investigated.

The elderly mice were randomly divided into control group, model group, remimazolam group, remimazolam + AMPK inhibitor Compound C group, with 8 mice in each group. The Morris water maze was used to detect the learning and memory ability of mice in each group. HE staining was used to detect pathological damage in hippocampal tissue. The expression of PINK1, Parkin, p62, Beclin-1, LC3Ⅱ/Ⅰ, p-AMPK/AMPK, PGC-1α, SIRT3 proteins in hippocampal tissue were detected by Western blot. The levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in hippocampal tissues were detected by kits.

For the escape latency period, the analysis of variance of the control group, model group, remimazolam group, and remimazolam + AMPK inhibitor Compound C group on the 1st-5th day of the last dose showed that the differences between the groups were statistically significant, and there was an interaction between groups and time points, and except for the first time point, there were statistically significant differences between the two groups, and there were significant differences between the control group, the model group, the remimazolam group, and the remimazolam + AMPK inhibitor Compound C group at all time points. Compared with the control group, the traversed original platform numbers and dwell time in the target quadrant shortened (P<0.05), and hippocampal tissue presented significant pathological damage, and the PINK1, Parkin, Beclin-1, LC3Ⅱ/Ⅰ, p-AMPK/AMPK, PGC-1α, SIRT3, SOD, GSH-Px in hippocampal tissue decreased whereas p62, MDA increased (P<0.05). Compared with the model group, the traversed original platform numbers and dwell time in the target quadrant prolonged (P<0.05), and pathological damage in hippocampal tissue alleviated, and the PINK1, Parkin, Beclin-1, LC3Ⅱ/Ⅰ, p-AMPK/AMPK, PGC-1α, SIRT3, SOD, GSH-Px in hippocampal tissue increased whereas p62, MDA decreased (P<0.05). Compound C partly reversed the effect of remimazolam (P<0.05).

Remimazolam alleviates the pathological damage of hippocampal tissue by promoting mitophagy and inhibiting oxidative stress, thereby improving the cognitive impairment of mice after fracture surgery, and its mechanism may be related to the activation of AMPK/PGC-1α/SIRT3 signaling pathway.