Effects Of Intranasal Insulin Infusion On Spatial Memory And Learning After Propofol Anesthesia In Rats

Objective:To explore whether intranasal infusion of insulin can improve spatial memory and learning impairments induced by anesthesia in rats.Methods:80 SD male rats(12-15 month age),Propofol(150mg/kg)was intraperitoneally injected into the rats for 5 consecutive days to establish the POCD model,and insulin(1.75U)was injected into the nasal cavity of the rats every day one week before anesthesia.The rats were divided into the prevention group from the beginning of anesthesia,the prevention group from the end of anesthesia,and the treatment group from the beginning to the end of anesthesia.Water maze test(Morris)was used to detect the change of cognitive function of rats in each group.The changes of phosphorylated Tau protein and a-βamyloid protein(a-β)in serum of rats were detected by enzyme-linked immunosorbent assay(ELISA),Hematoxylin-eosin staining(HE)was used to observe the apoptosis of hippocampal neurons in each group.Results:(1)There was no significant difference in the quality of rats in each group before anesthesia(P>0.05).(2)Comparison of positioning cruise experiment results: On the first day of the experiment,there was no significant change in positioning cruise experiment between the insulin treated groups(P,T,PT)and the normal saline control group(N),and the difference was not statistically significant(P > 0.05);there was no statistically significant difference between the insulin treated groups(P,T,PT)(P >0.05).On the second day of the experiment,the comparative positioning cruise experiment time of P,T,PT group and N group was shortened,and the difference was statistically significant(P < 0.05),while there was no statistically significant difference between P,T and PT groups(P > 0.05).The comparative positioning cruise experiment time of P,T,PT group and N group was significantly shortened on the third and fourth days of the experiment.The difference was statistically significant(P< 0.05),while there was no significant difference among groups P,T and PT(P >0.05).(3)Comparison of test results of space exploration experiments:The number of crossing the platform in P,T and PT groups was significantly increased compared with that in N group,and the difference was statistically significant(P < 0.0001).There was no statistically significant difference among groups of P,T and PT(P >0.05).The swimming time and distance in the target quadrant of the insulin treated groups(P,T and PT)were longer than that of the normal saline control group(N).The difference was statistically significant(P < 0.01),and there was no statistically significant difference among P,T and PT groups(P > 0.05).(4)Comparison of serum phosphorylated Tau protein(P-Tau)by ELISA assay:Phosphorylated Tau protein(P-Tau)did not change significantly between insulin treatment groups(P,T,PT)and normal saline control group(N)on the day before anesthesia,and the difference was not statistically significant(P > 0.05).There was no statistically significant difference between P,T,PT groups(P > 0.05).On the first and seventh days after anesthesia,-Tau protein in group N was significantly higher than that in group P,T and PT,and the difference was statistically significant(P < 0.0001),while there was no statistically significant difference among groups P,T and PT(P > 0.05).(5)Comparison of the results of β-amyloid protein(A-β)test by ELISA:There was no significant difference in β-amyloid protein(a-β)between the insulin treated groups(P,T,PT)and the normal saline control group(N)on the day before anesthesia(P >0.05).The β-amyloid protein in the N group was higher than that in the P,T and PT groups on the first day after anesthesia,and the difference was statistically significant(P < 0.0001).On the seventh day after anesthesia,beta-amyloid protein in group N was significantly higher than that in groups P,T and PT,and the difference was statistically significant(P < 0.0001),while there was no statistically significant difference among groups P,T and PT(P > 0.05).(6)Comparison of HE staining test results: compared with the normal saline control group(N),the hippocampal cells in the prevention group(P),treatment group(T)and prevention and treatment group(PT)were closely arranged with clear membrane,while the hippocampal cells in the control group were disordered,necrosis and nuclear pyknosis.Conclusions:Insulin injection into the nasal cavity can prevent the damage of spatial memory and learning ability caused by anesthesia in rats.Intrasonasal infusion of insulin can reduce the deposition of phosphorylated tau protein(P-tau)and beta-amyloid protein(a-β)induced by anesthesia.Intrasonasal infusion of insulin can reduce the apoptosis of hippocampal neurons in rats.