Abstract: Objective: To explore the improvement of glycyrrhetinic acid (GA) on the damage of synaptic ultrastructures of hippocampus induced by realgar in the mice, and to clarify the related mechanisms.Methods: Sixty ICR mice were randomly divided into three groups with twenty mice in eachgroup: control group (intragastrically treated with 0.5 % CMC-Na), realgar group (intragatrically treated with realgar 1.35 g·kg^-1), and GA intervention group (intragastrically administered with GA 48 mg·kg^-1 and realgar 1.35 g·kg^-1). The mice were administrated once a day for eight consecutive weeks. The cognitive and memory abilities were tested using object recognition task (ORT).The levels of glutathione(GSH) in the hippocampus in the mice in various groups were detected. The changes of the ultrastructures of synapse in hippocampal CA1 region, the width of synaptic cleft, the length of synaptic active zone, the thickness of post synaptic density (PSD) and the curvature of synaptic interface were observed by transmission electron microscope.Results: Compared with control group, the preferential index (PI) for the novel object and the level of GSH in the hippocampus tissue of the mice in realgar group were significantly decreased (P<0.05);compared with realgar group, the PI for the novel object had no obvious changes and only showed the increasing tendency (P>0.05),and the level of GSH in the hippocampus tissue of the mice in GA intervention group was significantly increased (P<0.05). Compared with control group, the synaptic structure in the hippocampal CA1 region of the mice in realgar group was fuzzy; the width of synaptic cleft was increased (P<0.01),the length of the synaptic active zone, the thickness of PSD and the curvature of synaptic interface were decreased (P<0.01).Compared with realgar group, the synaptic structure in the hippocampal CA1 region of the mice in GA intervention group was clear and complete;the width of synaptic cleft was decreased (P<0.05), the length of the synaptic active zone and the thickness of PSD were significantly increased (P<0.05); the curvature of synaptic interface had no obvious change, only showed the increasing tendency (P>0.05).Conclusion: Realgar can change the synaptic structural parameters and cause deficits in cognitive and memory abilities. GA can alleviate the abnormal ultrastructural changes in the hippocampal synapses of the mice.

Key words: glycyrrhetinic acid, realgar, hippocampus, synapses, ultrastructure