FPS-ZM1对糖基化终产物诱导海马区Aβ代谢水平的影响  

Effects of FPS-ZM1 on the metabolism of Aβ induced by advanced glycation end products in hippocampus

作　　者：孙梦晗[1] 洪艳[1] 侯训尧[1] 马莹娟 申超[1] 殷青青[1] 陈健[1] 罗鼎真[1] 刘雪平[1] 

机构地区：[1]山东大学附属省立医院老年神经科,山东济南250021

出　　处：《山东大学学报（医学版）》2014年第7期1-6,10,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(30971036);山东省自然科学基金(Y2008C13)

摘　　要：目的观察RAGE受体阻断剂FPS-ZM1对高级糖基化终产物(AGEs)诱导海马区Aβ及相关代谢因素表达水平的影响。方法将40只大鼠随机分为生理盐水组(NC组)、FPS-ZM1对照组、AGEs组和FPS-ZM1组。向大鼠海马区注射AGEs,以建立AGEs脑损伤模型,并用FPS-ZM1干预。造模3周后HE染色观察海马区神经元病理改变;Morris水迷宫实验检测逃逸潜伏期(EL);蛋白印迹法检测各组RAGE、p-NF-κB、BACE1和APP的蛋白表达;酶联免疫吸附法检测各组Aβ1-40、Aβ1-42的水平。结果与NC组、FPS-ZM1对照组相比,AGEs组及FPS-ZM1组海马神经元排列疏松,p-NF-κB、BACE1和APP的蛋白表达和Aβ1-40、Aβ1-42浓度均升高(P<0.01);但FPS-ZM1组上述改变均明显低于AGEs组,同时AGEs组RAGE表达明显增强,EL显著延长(P<0.01),但FPS-ZM1组与NC组和FPS-ZM1对照组相比无统计学差异(P>0.05)。结论 RAGE受体阻断剂FPS-ZM1能通过降低Aβ及相关代谢因素的表达水平,有效抑制AGEs所致的脑损伤。Objective To detect the effects of RAGE inhibitor FPS-ZM1 on the metabolism of Aβ and related factors induced by advanced glycation end products（ AGEs） in hippocampus. Methods A total of 40 Wistar rats were randomly divided into normal control group（ NC group）,FPS-ZM1 control group,AGEs group and FPS-ZM1 group.AGEs were injected into hippocampus to produce brain injury models of AGEs and the rats were intervened by FPSZM1. After the animal models were constructed for 3 weeks,HE staining was used to detect the pathological change.The escape latency（ EL） was assayed with Morris water maze test. Western blotting was performed to detect the expression of RAGE,p-NF-κB,BACE1 and APP protein expression. The levels of Aβ1-40and Aβ1-42of each group were measured by enzyme linked immunosorbent assay. Results Compared with NC group and FPS-ZM1 control group,the neurons in hippocampus of AGEs group and FPS-ZM1 group arranged more irregularly,and the protein expressions of p-NF-κB,BACE1 and APP,and the concentrations of Aβ1-40and Aβ1-42were obviously increased（ P 〈0. 01）,but each index of FPS-ZM1 group was evidently lower than that of the AGEs group. Meanwhile,in the AGEs group,theprotein expression of RAGE was significantly higher and the EL was also longer（ P〈 0. 01）,but the above indexes in FPS-ZM1 group were not significantly different（ P〉 0. 05）. Conclusion The RAGE inhibitor FPS-ZM1 can reduce the metabolism of Aβ and related factors to effectively suppress the AGEs brain injury.

关 键 词：高级糖基化终末产物 阿尔兹海默病 RAGE受体阻断剂 Β分泌酶 AΒ 

分 类 号：R749.1[医药卫生—神经病学与精神病学]