戊二酰亚胺类抗生素S-632A对D-半乳糖老化小鼠海马神经元Aβ及其相关蛋白表达的影响  

Effect of glutarimide antibiotic S-632A on expressions of β-amyloid and the related proteins in hippocampus of mice with D-galactose-induced aging

作　　者：王婷[1] 桂冠[2] 赵春燕[1] 徐榕[1] 李电东[1] 邓洪斌[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所,北京100050 [2]南京医科大学第一附属医院,南京210029

出　　处：《中国新药杂志》2008年第12期1022-1025,共4页Chinese Journal of New Drugs

基　　金：973国家重点基础研究发展计划(200707400);国家自然科学基金资助项目(30600659)

摘　　要：目的:观察戊二酰亚胺类抗生素S-632A对D-半乳糖老化小鼠模型(DGAM)海马神经元β-淀粉样肽(β-amyloid,Aβ)及其相关蛋白表达的影响。方法:采用免疫组织化学染色和免疫印记方法,检测DGAM海马神经元Aβ、β-分泌酶(Beta-site APP cleaving enzyme,BACE)、内质网Aβ结合蛋白(Endoplasmicreticulum amyloidβpeptide binding protein,ERAB)和早老蛋白1(Presenilin-1,PS-1)的表达水平,并观察应用戊二酰亚胺类抗生素S-632A对DGAM海马神经元的保护作用。结果:对照组小鼠海马神经元Aβ及其相关蛋白BACE,ERAB和PS-1表达量少,而DGAM小鼠海马神经元Aβ及其相关蛋白表达水平明显增加,与对照组比较差异具有高度显著性(P<0.01),S-632A组上述各种蛋白的表达结果与对照组接近。结论:DGAM小鼠海马神经元存在着Aβ及其相关蛋白BACE,ERAB和PS-1表达的上调,S-632A可明显改善模型动物中上述蛋白的异常表达,对小鼠神经元具有营养和保护作用。Objective： To investigate the effect of glutarimide antibiotic S-632A on the expressions of β- amyloid （Aβ） and its related proteins in the hippocampus in D-galactose-induced aging of murine model （DGAM）. Methods： The expression levels of Aβ, beta-site APP cleaving enzyme （BACE）, endoplasmic reticulum amyloid β peptide binding protein （ERAB） and presenilin-1 （PS-1） of DGAM were determined with immunohistochemical staining and Western blotting. The protective effect of S-632A was also observed. Results： The ex- pression levels of Aβ and its related proteins was obviously increased in the hippocampus of DGAM as compared with the control group （P 〈 0.01 ）. Treatment with S-632A reduced the increased expressions; the expression levels were as same as those in the controls. Conclusion： The expression levels of Aβ and its related proteins are up-regulated in the hippocampus of DGAM, while S-632A normalizes the expression of those proteins and protects the mouse neurons.

关 键 词：戊二酰亚胺类抗生素 S-632A D-半乳糖老化小鼠模型(DGAM) Β-淀粉样肽 Β-分泌酶 内质网Aβ结合蛋白 早老蛋白-1 阿尔兹海默病 

分 类 号：R978.1[医药卫生—药品]