The Effects Of β-sheet Breaker Peptide H102 On APP Metabolic Enzymes In Brain Of Double Transgenic AD Mice

Objective:To observe the effect of β-sheet breaker peptide H102 on Aβ、APP metabotropic enzymes and cognitive ability of AD mice in APP/PS1 double transgenic AD mice.Methods:1.Thirty 6-month APP / PS1 double transgenic mice were randomly divided into AD group and H102 group.Fifteen C57BL/6J mice with the same age and same background were used as control group.Through the nasal administration method,At the same time,once a day,H102 mice were given H102 solution(5.8 mg / kg)5μl,AD group and the control group given the auxiliary solution 5μl After 30 days of continuous administration,the learning and memory abilities of the mice were tested by the new object recognition experiment and the Morris water maze test.2.After the completion of the behavioral experiment,10% intraperitoneal injection of chloral hydrate,PBS perfusion,the mice were sacrificed,and the brain was taken on the ice.The brain tissue was placed in 4% of the paraformaldehyde prepared in advance,and the cells were embedded for 24 hours.The expression of Aβ,ADAM10,ADAM17,BACE1,PS1,PEN-2 and APH1-a protein in the brain were detected by immunohistochemistry.The other half of the hippocampus and cortex after separation,do the mark first stored in liquid nitrogen,and then removed from the liquid nitrogen into the-80 ℃ refrigerator to detect the expression of Aβ protein and the expression of ADAM17,BACE1,PS1,PEN-2,APH1-a protein use ELISA and Western blot.Results:1.Novel object recognition : AD group compared to the control group,the new object identification index was significantly reduced(P <0.05);H102 group compared to AD group,the new object identification index was significantly increased(P <0.05).H102 group compared with the control group,no significant difference(P>0.05).2.Positioning navigation experiment: Compared with the control group,the escape latency was significantly prolonged(P <0.05);Compared with AD group,the escape latency was significantly shorter than that of H102 group(P <0.05);Then the space exploration experiment,AD group compared to the control group,the third quadrant residence time and the number of times across the hidden platform was significantly reduced,the water into the angle significantly increased(P<0.05).H102 group compared to AD group,the third quadrant dwell time and the number of times across the hidden platform increased significantly,into the water toward the angle of reduction(P <0.05).H102 group compared with the control group,no significant difference(P>0.05).3.Immunohistochemistry test: The expression of BACE1,PS1,PEN-2 and APH1-a in AD group was significantly higher than that in control group,and the protein expression of ADAM10 and ADAM17 was significantly lower than that of control group(P<0.05);The levels of Aβ,BACE1,PS1,PEN-2 and APH1-a in H102 group were significantly lower than those in AD group,and the expression of ADAM10 and ADAM17 protein was significantly higher than that of AD group(P<0.05);H102 group compared with the control group,no significant difference(P>0.05).4.Western blot test: The expression of BACE1,PS1,PEN-2 and APH1-a in the brain of AD group was higher than that in the control group,and the expression of ADAM10 and ADAM17 protein was lower than that of the control group(P<0.05);The expression of BACE1,PS1,PEN-2 and APH1-a in H102 group was significantly lower than that in AD group,and the expression of ADAM10 and ADAM17 protein was significantly higher than that of AD group(P<0.05).H102 group compared with the control group,no significant difference(P>0.05).5.Aβ protein test results: Immunohistochemistry and ELISA assay were all shown,AD group compared with the control group,the expression of Aβ protein was significantly increased(P <0.05);Compared with AD group,the expression of Aβ was significantly reduced(P <0.05).H102 group compared with the control group,no significant difference(P>0.05).Conclusions:β-sheet breaker peptide H102 can affect the metabolism of APP in brain of AD mice,reduce the expression of Aβ,BACE1,PS1,PEN-2 and APH1-a protein,increase the content of ADAM10 and ADAM17 protein,reduce the production of Aβ,H102 can enhance the learning and memory ability of AD mice.