Effect Of Preconditioning With Liver X Receptor Agonist On Hippocampal Neurogenesis In Aged Mice

Objiective: To observe the postoperative expression changes of mouse hippocampal liver X-? receptor(LXR-?),and preoperative LXRs agonist pretreated mice were used to observe the changes of postoperative learning and memory as well as hippocampal neurogenesis.To explore the intrinsic relationship between hippocampal LXRs expression,hippocampal neurogenesis and postoperative cognitive function,provide a theoretical basis for LXRs agonist treatment of postoperative cognitive dysfunction(POCD).Methods: Male Kunming mice were randomly divided into a control group(N group),a surgical group(OP group),and a surgery + T0901317 group(OP+T0 group),with a total of 24 in each group(each of which was referenced the time of after surgery,there were divided into 0 days,3 days,7 days,and 14 days,6 in each group).The specific grouping and processing methods are as follows:(1)The expression of LXR-? receptor in hippocampus was detected after operation: mice in group N were not treated,and mice in group OP were surgically treated.The mice were sacrificed on day 0,day 3,day 7 and day 14 after operation to obtain hippocampus.Western Blot was used to detect the expression of LXR-? in the hippocampus.(2)Postoperative cognitive function was detected: N mice were not treated,and OP+T0 mice were given LXRs agonist T0901317(30 mg/kg,intraperitoneal injection,once a day,for 7 days)7 days before surgery.Mice in the OP group received an equal amount of DMSO(solvent control)intraperitoneally at the same time.Three groups of mice were subjected to swimming training(training for 4 days)after the fourth day of administration.The OP group and the OP+T0 group were surgically treated after the end of the swimming training.The mice in the N group,OP group and OP+T0 group were tested for learning and memory on the 0th,3rd,7th and 14 th day after operation.(3)Postoperative hippocampal neurogenesis was detected: Grouping and treatment were the same as the second step.On the fourth day(ie,4 days before surgery),the mice in the three groups were labeled with BrdU(50 mg/kg,intraperitoneal injection,twice a day,for 4 days).After the intraperitoneal injection and swimming training,the mice in the OP group and the OP+T0 group were operated.The mice were sacrificed at 0,3,7 and 14 days after operation,and the number of BrdU+/DCX+ cells in the hippocampus of the three groups of mice was detected by immunofluorescence.RESULTS:(1)The expression of LXR-? in the hippocampus of mice decreased after surgical.(2)After the operation,the mice's water maze test extended the escape latency,and the number of crossing platforms was reduced.The pretreatment of liver X receptor agonist T0901317 before surgery could be significantly improved this sorry condition.(3)The hippocampal neurogenesis was reduced after surgery.Pretreatment with liver X receptor agonist T0901317 promoted neurogenesis in the hippocampus after operation in mice.Conclusion: Surgery can cause cognitive decline in mice.Activation of LXRs can improve postoperative cognitive function in mice.The mechanism may be achieved by promoting hippocampus neurogenesis.