Objective:To explore the improvement and its mechanism of minocycline on sevoflurane anesthesia induced cognitive dysfunction in aged mice.Methods:Totally 75 aged clean-grade C57BL/6 mice were randomly divided into control (Con) group( n=25), sevoflurane (Sev) group( n=25) and sevoflurane + minocycline (Sev+ Min) group( n=25). Anesthetic injury was induced by 3% sevoflurane (2 h/d for 3 days) in Sev group. Minocycline (50 mg/kg) was injected intraperitoneally first, and then 3% sevoflurane (2 h/d for 3 days) anesthesia was performed in Sev+ Min group. Saline alone was injected intraperitoneally (once a day for 3 days) in Con group.The spatial memory function was detected by Morris water maze experiments. BrdU was used to label new neuron and the proliferation was observed by immunohistochemistry. The field excitatory postsynaptic potential (fEPSP) slope was measured in hippocampal dentate gyrus (DG) region of isolated brain slices by electricphysiological technique.The data were analyzed by repeated measures analysis of variance and SNK-q test using SPSS 21.0 software. Results:Results from positioning navigation experiment showed that the group×time interaction effect of mice was significant( F=15.65, P<0.01). On the 6th day after anesthesia, compared with Con group, the escape latency of the original platform in Sev group was significantly increased ( q=4.35, P<0.05) in space exploration experiment, while the target quadrant time ratio ( q=6.15, P<0.05))and the mean annulus crossings ( q=6.45, P<0.05) were significantly decreased. Compared with Sev group, the escape latency in Sev+ Min group was significantly decreased ( q=3.01, P<0.05), while the target quadrant time ratio ( q=3.21, P<0.05) and the mean annulus crossings ( q=3.48, P<0.05) were significantly increased. In immunohistochemistry experiment, the number of BrdU positive cells in Sev group was significantly reduced ((227.45±43.25), q=8.67, P<0.01) compared with Con group (355.87±62.58). Compared with Sev group, the number of BrdU positive cells in Sev+ Min group was significantly increased ((338.73±47.27), q=8.68, P<0.01). In electricphysiological test, the fEPSP slope after high frequency stimulation in Sev group ((126.83±25.67)%, q=6.18, P<0.01)) was significantly lower than that in Con group((214.38±43.42)%). In Sev+ Min group, the fEPSP slope was significantly higher ((178.49±32.67)%, q=3.64, P<0.05) than that in Sev group. Conclusion:Sevoflurane anesthesia can induce the short-term cognitive dysfunction in aged mice, and its mechanism is related to inhibiting neuron proliferation and synaptic plasticity. Minocycline can alleviate the damage caused by sevoflurane.