海马高级糖基化终末产物受体和β-淀粉样前体蛋白裂解酶表达增加与自发性高血压大鼠认知功能损害相关性研究

Relationship between increased expression of receptor for advanced glycation end-products andβ-site APP cleaving enzyme in hippocampus and cognitive impairment in spontaneously hypertensive rats

目的:研究海马区域RAGE蛋白与BACE蛋白异常表达与自发性高血压大鼠(SHR)认知功能损害之间的关系。方法:采用SHR大鼠与正常血压大鼠(NWR)进行相关研究,增强型磁共振成像(MEMRI)检测大鼠海马脑区生理活动。采用Morris水迷宫、新事物识别实验分析大鼠的认知功能。使用Western blot分析海马区域高级糖基化终末产物受体(RAGE)与β-淀粉样前体蛋白裂解酶(BACE)蛋白的表达水平。使用免疫蛋白反应对NWR以及SHR大鼠脑切片进行Aβ斑块染色。结果:SHR相比NWR组,大鼠海马脑活动明显减少(0.698与1.499,P<0.01);Morris水迷宫中,SHR组大鼠在测试阶段对平台的寻找时间显著延长(35.3与12.2,P<0.01);新事物识别实验中,SHR组大鼠对新物体的探索时间显著降低(13.7与31.5,P<0.01);通过检测NWR与SHR组中大鼠海马区域RAGE与BACE蛋白的表达水平,发现RAGE与BACE的表达均有显著升高(0.407与0.789,P<0.05;0.733与1.502,P<0.01);对两组大鼠进行切片染色,发现SHR大鼠海马区域有大量Aβ阳性的斑块沉积。结论:SHR大鼠海马功能低下导致认知功能受损,与海马区域RAGE、BACE蛋白表达增加、Aβ斑块沉积有关。

Objective:To explore the relationship between increased expression of receptor for advanced glycation end-products(RAGE)andβ-site APP cleaving enzyme(BACE)in hippocampus and cognitive impairment in spontaneously hypertensive rats(SHR).Methods:The SHR and normotensive wistar rats(NWR)was used in this research.MEMRI was applied to detect the hippocampus brain activity.Furthermore,Morris water maze and novel objective recognition tests were used to analyze the cognitive function in NWR and SHR.Western blot was used to analyze the expression levels of RAGE and BACE proteins.The brain sections of NWR and SHR were subjected to Aβplaque staining by immunoenzymatic reaction.Results:Compared with NWR group,the hippocampus brain activity in SHR group decreased significantly(P<0.01);in Morris water maze test,SHR group expended longer time in finding the platform(P<0.01);in novel object recognition test,SHR group showed fewer interest in sniffing or touching the novel object(P<0.01).The expression levels of RAGE and BACE proteins in the hippocampus of rats in NWR and SHR groups were significantly increased(all P<0.01).Furthermore,it was found that there was massive Aβplaques deposit in the hippocampus in SHR group.Conclusion:Decreased hippocampal function in SHR leads to impaired cognitive function,which is related to the increased expression of RAGE and BACE proteins and Aβplaque deposition in hippocampal region.