Intranasal Insulin Improves Postoperative Cognitive By Promoting Hippocampal Neurogenesis

Objective: This study investigated whether Intranasal insulin administration can improve postoperative cognitive in Kunming mice by promoting hippocampal neurogenesis,to explore possible mechanisms.Methods: The elder Kunming mice were used as experimental subjects.The safe dose of insulin intranasal inhalation was first determined,Intranasal insulin dose gradients of 0.0?0.5? 1.0 and 2.0 IU were set under non-surgical conditions to detect blood glucose in mice 3 hours after administration.Further experiments were divided into blank group,surgery group and surgery + insulin group.Each group contained three subgroups of 1,2,and 3.The surgery group,surgery + insulin group were simulated by laparotomy and postoperative blood glucose was tested.The mice in the surgery+insulin group were administered with insulin intranasal dripping three hours before surgery and three days after surgery.The mice in the surgery group and the blank group were treated with the same amount of normal saline.Novel object recognition task was performed on the 7th day after surgery in the blank group,the surgery group,and the surgery + insulin group.The brain tissue of the second subgroup was taken 7 days after surgery.The number of newborn neurons in the hippocampal dentate gyrus was counted by fluorescence microscopy.The second subgroup of brain tissue sections were selected for immunohistochemistry,and the expression of GSK3? was observed.In the third subgroup,Western Blot was used to obtain protein bands 7 days after surgery,and the gray value was analyzed by Image J software to compare the difference of p-GSK3?.Results: 1.Kunming mice with a single intranasal insulin dripping 0.5 or 1 IU had no significant effect on blood glucose in mice,2 IU had an effect;a single 1 IU administration had no significant effect on postoperative blood glucose in mice.2.During the training period,there was no significant deviation in the postoperative operation between the surgical group and the surgery+insulin group.During the test period,the interest preference of the experimental group for exploring new objects after surgery was significantly higher than that of the surgery group.3.The number of DCX/Brdu positive cells in the hippocampus of the mice treated with insulin intranasal dripping was higher than that of the surgery group.4.The results of immunohistochemistry showed that there was no significant change in the total amount of GSK3? in hippocampal dentate gyrus after intranasal insulin treatment.The Western Blot analysis indicated that the amount of p-GSK3? in hippocampus of intranasal insulin-treated mice increased after operation.Conclusion:Intranasal insulin dripping improves postoperative cognitive function in Kunming mice by promoting hippocampal neurogenesis.