Role of hippocampal cannabinoid receptor 2 in postoperative cognitive dysfunction in mice / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of hippocampal cannabinoid receptor 2 (CB2R) in postoperative cognitive dysfunction (POCD) in mice.Methods Fifty-four healthy male C57BL/6 mice,aged 12-16 weeks,weighing 20-30 g,were divided into 3 groups (n=18 each) using a random number table:control group (group C),group POCD and POCD plus CB2R agonist JWH133 group (group POCD+J).The mice were subjected to an intramedullary fixation for tibial fracture under 1.5％ isoflurane anesthesia to establish POCD model.In group POCD+J,2 mg/kg JWH133 was injected intraperitoneally at a total volume of 10 ml/kg after emergence from anesthesia and then the injection was repeated once a day until the 7th day after surgery.Open field test was carried out on 1 day before surgery and 1,3 and 7 days after surgery to evaluate the locomotor activity.Fear conditioning test was carried out at 15 min after completion of open field test.Mice were sacrificed at 2 h after the end of behavioral test,and the hippocampus was harvested for determination of the expression of tumor necrosis factor-alpha (TNF-α),interleukin-1beta (IL-1β),monocyte chemotactic protein-1 (MCP-1) and CB2R (by Western blot) and expression of CD11b in hippocampal tissues (by immunofluorescence).Results There was no significant difference in the total exploring distance in open field test,percentage of freezing time in contextual fear conditioning test or percentage of freezing time in tone-fear conditioning text at each time point among the three groups (P＞0.05).Compared with group C,the percentage of freezing time in contextual fear conditioning test was significantly decreased,and the expression of TNF-α,IL-1β,MCP-1,CD11b and CB2R was up-regulated after surgery in group S (P＜0.05).Compared with group S,the percentage of freezing time in contextual fear conditioning test was significantly increased,and the expression of TNF-α,IL-1β,MCP-1,CD11band CB2R was down-regulated after surgery in group S+J (P＜ 0.05).Conclusion Activation of hippocampal CB2R may be involved in the endogenous protective mechanism of POCD in mice,and the mechanism is related to inhibiting activation of hippocampal microglia and attenuating central inflammatory responses.