β片层阻断肽H102对双转基因AD小鼠海马脑区APP代谢酶的影响  

Effect of β sheet blocking peptide H102 on APP metabolic enzymes in hippocampal brain of double transgenic AD mice

作　　者：蒋方[1] 孙凤仙[1] 徐淑梅[1] 

机构地区：[1]天津医科大学生理学教研室,天津300070

出　　处：《中国应用生理学杂志》2017年第4期299-303,共5页Chinese Journal of Applied Physiology

基　　金：国家科技重大专项基金资助(2009ZX09103029);天津市科技支撑重点项目基金资助(16YFZCSY01000)

摘　　要：目的:探讨β片层阻断肽H102对APP/PS1双转基因小鼠(AD小鼠)海马脑区β淀粉样蛋白前体蛋白(APP)代谢分泌酶以及学习记忆能力的影响。方法:将6月龄大小的30只AD模型小鼠随机分为AD组和H102组,相同月龄、数量和背景的C57BL/6J小鼠作为对照组(n=15)。H102组每日经鼻腔给予H102溶液(5.8 mg/kg)5μl,对照组及AD组每日给予辅料溶液5μl。给药30 d后,使用Morris水迷宫的方法检测各组小鼠的空间记忆能力变化,采用免疫组织化学方法及Western blot技术测定海马脑区α分泌酶(ADAM10和ADAM17)、β分泌酶(BACE1)及γ分泌酶(PS1,APH1a,PEN2)在小鼠海马中的表达。结果:与对照组比较,AD组小鼠海马脑区BACE1、PS1、PEN-2、APH1-a蛋白表达显著升高,ADAM10、ADAM17蛋白表达显著降低(P<0.05);与模型组相比,H102能够明显提高AD小鼠的空间学习记忆能力,明显降低海马脑区BACE1、PS1、PEN-2、APH1-a蛋白的表达,明显提高ADAM10、ADAM17蛋白的表达(P<0.05)。结论:β片层阻断肽H102能够减少海马脑区Aβ的生成,提高海马脑区α分泌酶的活性,降低β和γ分泌酶的活性,改善AD小鼠的学习记忆能力。Objective： To investigate the effect of β-sheet breaker peptide H102 on APP associated secretase in the hippocampus brain regions of APP/PS1 double transgenic mice（ AD mice）. Methods： Thirty 6-month-old APP/PS1 double transgenic mice were randomly divided into AD group and H102 group,a group of C57 BL/6 J mice with the same age,number and background was set as controls（ n = 15）.H102（ 5.8 mg/kg） 5 μl was infused by intranasal administration to mice in H102 treatment group,and equal volume of blank solution of H102 was given to mice in control group and AD group. The ability of spatial reference memory was tested by Morris water maze after 30 days of treatment. And then immunohistochemistry tests and Western blot were used to detect the content of α-secretase（ ADAM10,ADAM17）,β-secretase（ BACE1）,γ-secretase（ PS1,APH1 a,PEN2） in the hippocampus brain regions. Results： Compared with the control group,the expression of BACE1,PS1,PEN-2 and APH1-a protein in the hippocampus of AD group were significantly increased,ADAM10,ADAM17 protein expression were significantly reduced（ P0.05）; Compared with the model group,H102 could significantly improve the spatial learning and memory ability of AD mice,significantly decreased the expression of BACE1,PS1,PEN-2 and APH1-a protein in the hippocampus,significantly increased the expression of ADAM10 and ADAM17 protein（ P 0. 05）. Conclusion： β sheet peptides blocked H102 can reduce the formation of Aβ in the hippocampus brain area,improve the activity of α-secretase in the hippocampus brain region,decrease the activity of β-and γ-secretase,improve the learning and memory ability of AD mice.

关 键 词：H102 APP α分泌酶 Β分泌酶 Γ分泌酶 阿尔茨海默病 APP/PS1双转基因小鼠 

分 类 号：R338.8[医药卫生—人体生理学]