| Objective By producing an animal model of POCD,observing the behavioral changes,and through biochemical,pathological,molecular biological and other techniques combined with clinical studies,we explored whether this drug could affect the cognitive function of rats by activating the IRS-PI3K-AKT-GLUT4 pathway.Methods Fifty clean grade aged SD male rats were randomly assigned to normal control group(Group C),POCD model group(group P)with low-dose administration group(group L)and high-dose administration group(Group H),positive control group(Group D).Trials started 7 days after all rats had acclimated to housing,and rats were trained in water maze location navigation starting 5 days before surgery.All rats underwent the Morris water maze navigation localization and spatial exploration experiments on the preoperative day 1 and postoperative days 1,3,5,and their learning and memory abilities were assessed.At the end of the water maze experiment,the rats were sacrificed to obtain arterial blood and hippocampal tissue.The m RNA levels of insulin receptor substrate-2(IRS-2),phosphotidylinositol 3-kinase(PI3K),serine threonine protein kinase(AKT),and glucose transport factor 4(GLUT4)were measured in the hippocampus by real-time PCR,and the expression of IRS-2 、p-IRS-2,PI3K、p-PI3 K,AKT、p-AKTand GLUT4、p-GLUT4 protein in hippocampus was detected by Western blot.Conclusion 1.Compared with group C,groups P,D,H,and L showed prolonged escape latency(P < 0.05)and decreased number of times to cross the platform(P < 0.05)at 1d,3d and 5d after surgery.Compared with group P,groups D,H,and L showed decreased escape latency and increased number of crossing the platform at all time points after surgery(P < 0.05).Within groups P,D,H,and L,escape latencies decreased(P < 0.05)and the number of times to cross the platform increased(P < 0.05)between 3 and 5days after surgery compared with 1 day after surgery and did not differ(P > 0.05)between 3 and 5 days after surgery.2.Compared with group C,the m RNA expression of IRS-2,PI3 K,AKT and GLUT4 in hippocampus of group P,group D,group H and group L were decreased(P < 0.05),and compared with group P,the m RNA expression of IRS-2,PI3 K,AKT and GLUT4 in hippocampus of group D,group H and group L were increased(P < 0.05).Compared with group D,the expression levels of IRS-2 and AKT in group L were higher,and the expression level of PI3 K in group L was higher(P < 0.05).AKT m RNA expression in group H was higher than that in group L(P < 0.05).There was no difference in the expression of PI3 K between group H and group D(P > 0.05),and there was no difference in the expression of GLUT4 among the three groups(P >0.05).3.Compared with group C,the p-IRS-2/IRS-2 ratio in the hippocampus of group P was higher than that of the control group(P < 0.05)Compared with group P,the ratio of the other three genes in group D,group H and group L was increased(P < 0.05),except the p-IRS-2/IRS-2 ratio was lower.Results Mongolian medicine Erdun wurile can improve the occurrence of postoperative cognitive dysfunction in rats.The mechanism may be related to insulin downstream signal molecule PI3 K and IRS-PI3K-AKT-GLUT4 signaling pathway. |
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