Effect Of β-sheet Breaker Peptid In PI3K/AKt Signaling Pathway On AD Model Mice

Objective:By observing the effects of H102 on APP/PS1 double transgenic mice behavior and the expression of APP and Aβ in brain by intranasal administration to study H102 treatment in Alzheimer’s disease;to investigate the feasibility of β-Sheet Breaker Peptide-H102 treatment for Alzheimer’s disease via 3-Kinase(PI3K,/Akt signaling pathway.Methods: 1.APP695V717/PS1 double transgenic mice and C57BL/6J mice were.raised in specific pathogen free(SPF,animal rooms at a temperature of 24±1℃ and a 12:12 h light/dark cycle(with lights on at 6:00 am,.The APP695V717I/PS1 transgenic mice were randomly divided into the model and H102 groups and C57BL/6J mice served as the control group.The treatment groups were intranasal administrated with H102 solution 5μl/d,while the model group and normal control group were treated with auxiliary material 5μl/d.After four weeks,the ability of spatila reference memory was tested by Morris Water Maze.2.All the mice were anesthetized by celiac injection with 10% chloral hydrate(400 mg/kg,and decapitated after processing all the mice were given PBS perfusion.Taken brains rapidly on the ice box.Take half of each mouse brain placed in-80 u C refrigerator.Portion of remaining specimens were fixed in paraformaldehyde solution containing 30% sucrose.Then embedded in paraffin,and made sequentially along coronal profile.Results: 1.Behavioral test: Mouse behavior was analyzed using the Morris water maze.The navigation test lasted five days,and no significant difference in escape latency was found between the H102 group and the normal control group(P﹥0.05,.However,from the second day to the fifth day there was a significant difference between the model group and the H102 group(P<0.05,.The time to finding the platform in both the H102 group and the normal control group decreased.On the sixth day,the platform was removed.The number of cross-platform periods and the original angle were indicators of memory and spatial learning in mice.The number of cross-platform periods between the normal control group and the model group was significantly different,which indicated that,compared to the normal control group,the mice in the model group found it more difficult to find the platform.The difference between the H102 group and the model group was significant,whereas no significant difference was observed between the H102 group and the normal control group(P﹥0.05,.2.Influence of H102 on the expression of ITGB5,PI3 K and Akt:(1)In the RT-PCR results,compared with the normal control group,the level of PI3 K m RNA in the model group were significantly lower,and the difference was significant between the H102 group and the model group.RT-PCR analysis revealed that the m RNA level of ITGB5 was down-regulated in the H102 group compared to the model group,and the difference was significant between the H102 group and the model group.(2)Western Blotting showed that the expression of PI3K(p85,was obviously increased in the H102 group compared with the model group(p<0.05,,and there was no significant difference between the normal control group and the H102 group.Compared with the model group,the expression of Akt was significantly enhanced in the H102 group(p<0.05,,and there was no significant difference between the normal control group and the H102 group.PI3 K and Akt immunohistochemical staining showed that positive cells in the cortex and hippocampus were increased in the H102 group compared with the model group(p<0.05,,and there was no significant difference between the normal control group and the H102 group.Conclusions: β-Sheet Breaker Peptide-H102 through ITGB5 via 3-kinase(PI3K,/Akt signaling pathway accelerated Aβ degradation treatment for Alzheimer’s disease.