Influence Of Aβ_1-40Oligomer On The Signal Path Of PI3-k/P K B In AD Model Mice

Objective:This study was designed to investigate the effects of Aβ1-40Oligomer on the cognitive function and Signal Path of Phosphatidy Inositol3-kinase/Protein Kinase B in model mice with Alzheimeri’s disease. Thus to explore the role of Aβ1-40Oligomer in the course of AD.Methods:according to the results of step-down test and body weight, Eight-week-old Kunming male mice(n=70) were randomly divided into5groups:control group, sham-operation group, AD modle group,Aβ Oligomer group and positive control(Insulin)group. Aβ Oligomer group was divided into low-dose, mid-dose and high-dose treatment groups. Each group contained10mice. AD modle group, Aβ Oligomer group and positive control group were given3mg/kg STZ intracerebroventricular (i.c.v) administration, sham-operation group was treated in the same way with equal-dose saline. After15days, step-down test was used to investigate the cognitive function.24hours before step-down test, each mouse of AP Oligomer group were different dose(0.015mg/kg、0.05mg/kg、0.15mg/kg) Aβ1-40Oligomer by intracerebroventricular (i.c.v) administration, positive control group were injected with Insulin, AD modle group and sham-operation group was treated in the same way with equal-dose saline. Then enzymelinked immunosorbent assay was used to observe the expression of Insulin receptor; Western blot was used to observe the expression of P-AKt, P-GSK-3β and P-Tau.Results:there was no significantly difference between control group and sham-operation group for the cognitive function, InR, P-PKB, P-GSK-3β, P-Tau in AD model group (P>0.05).Compared with control group, the cognitive function in AD model group was weaken (P<0.05), the expression of P-Tau was high (P<0.05). Compared with AD model group the cognitive function in Aβ Oligomer group was weaken (P<0.05),the expression of InR、P-PKB、P-GSK-3β was fewer (P<0.05), P-Tau was high (P<0.05). the cognitive function in IR group was high (P<0.05); the expression of InR、P-PKB、P-GSK-3β was high (P<0.05); the expression of P-Tau was fewer (P<0.05). Compared with IR group, groupthe cognitive function in Aβ Oligomer group was weaken (P<0.05),the expression of InR、 P-PKB、P-GSK-3β was fewer (P<0.05), P-Tau was high (P<0.05). Compared with Aβ Oligomer group each other by low-dose, mid-dose and high-dose treatment groups. With the dose from low to high.the cognitive function was weaken (P<0.05), the expression of InR、 P-PKB、P-GSK-3β was fewer (P<0.05), P-Tau was high (P<0.05)Conclusion:1. Aβ1-40Oligomer can inhibited the cognitive function of AD mice.2. Aβ1-40Oligomer can inhibited the Signal Path of Phosphatidy Inositol3-kinase/Protein Kinase B4. The mechanism of Aβ1-40Oligomer inhibited the cognitive function of AD mice and inhibited the Signal Path of Phosphatidy Inositol3-kinase/Protein Kinase B might be connected with the Aβ1-40Oligomer inhibited the expression of InR、P-PKB、P-GSK-3β of AD mice and inhibited the Signal Path of Phosphatidy Inositol3-kinase/Protein Kinase B, thus aggravate the expression of P-Tau and finally aggravate the course of AD.