Effect of α-ketoglutarate on postoperative delirium in aged mice / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of α-ketoglutarate (AKG) on postoperative delirium (POD) in aged mice.Methods:Eighty male C57BL/6N mice, aged 18 months, weighing 30-35 g, were divided into 4 groups ( n=20 each) using a random number table method: control+ solvent group (group C), control+ AKG group (group C+ AKG), surgery+ solvent group (group S) and surgery+ AKG group (group S+ AKG). Dimethyl 2-oxoglutarate 0.6 mg/kg was injected intraperitoneally for 3 consecutive days before surgery in C+ AKG and S+ AKG groups, while the equal volume of normal saline was given in C and S groups.Exploratory laparotomy was performed under anesthesia with isoflurane to establish POD model.The behaviors of mice in each group were tested at 24 h before surgery and 6, 9 and 24 h after surgery using buried food test (the latency to eat food), open field test (total distance, latency to the center, time and freezing time spent in the center) and Y maze test (duration in the novel arm and the number of entries into the novel arm), respectively.Then the animals were sacrificed at 6 h after operation, hippocampal tissues were removed for determination of the expression of microglia-specific marker ionized calcium binding adaptor molecule-1 (Iba-1), the number of Iba-1 positive cells (using immunofluorescence staining), and the expression of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in hippocamapus (by Western blot). Results:Compared with group C, the latency to eat food at eath time point was significantly prolonged, latency to the center at 6 and 9 h after surgery was prolonged, time spent in the center at 6 and 9 h after surgery was shortened, freezing time at 6, 9 and 24 h after surgery was shortened, the number of entries into the novel arm at 6 and 9 h after surgery was decreased, duration in the novel arm at 6 h after surgery was shortened, the expression of Iba-1 was up-regulated, the number of Iba-1 positive cells was increased, and the expression of IL-1β and TNF-α in hippocampus was up-regulated in group S ( P<0.05), and no significant change was found in the behaviors indexes in group C+ AKG ( P>0.05). Compared with group S, the latency to eat food at each time point was significantly shortened, latency to the center at 9 h after surgery was shortened, time spent in the center at 6 and 9 h after surgery was prolonged, freezing time at 9 and 24 h after surgery was prolonged, the number of entries in the novel arm at 9 h after surgery was increased, the expression of Iba-1was down-regulated, the number of Iba-1 positive cells was decreased, and the expression of IL-1β and TNF-α in hippocampus was down-regulated in group S+ AKG ( P<0.05). Conclusion:AKG can alleviate POD, and the mechanism may be related to inhibiting the activation of microglia and and thus reducing inflammatory responses in aged mice.