中文摘要：

目的通过研究糖基化终末产物（AGEs．BSA）对培养的人神经母细胞瘤细胞（SH。SY5Y细胞）8．淀粉样蛋白（Aβ）的生成，以及淀粉样前体蛋白（APP）及相关酶-p-分泌酶（BACEl）、1-分泌酶（PSl）的表达的影响，在体外水平探讨AGEs-BSA在阿尔茨海默病（AD）发病中的作用及其可能的机制。方珐以培养的SH．SYSY细胞为模型，将细胞随机分为4组。用MIT实验得到的AGEs-BSA最佳干预时间及浓度干预细胞，用免疫细胞化学方法及ELISA方法观察及检测各组细胞内Aβ1-40、Aβ1.42表达，用免疫印迹法检测各组细胞内APP、BACEl、PSl变化。结果BSA组与空白对照组相比APP、BACEl、PSl、Aft的表达无明显差异（P〉0．05）；AGEs-BsA组与BSA组相比APP、BACEl、Psl、AB的表达明显增加（P〈0．05）；AGEs-BSA＋抗RAGE中和抗体组APP、BACEl、PSl、Aft的表达较单纯AGEs—BSA组明显减少（P〈0．05），但仍高于BSA组（P〈0．05）。结论糖基化终末产物能够促使sH-SYSY细胞中舢＇P的表达增加，并通过上调BACEl、PSl的活性使Aβ生成增加。通过阻断其与特异性受体RAGE的结合可以部分减少APP、BACEl、PSl及Aβ的表达和生成。

英文摘要：

Objective To investigate the effect of advanced glycation end products （AGEs） on expressions of the β- amyloid protein （Aβ） and its related enzymes in cultured SH-SY5Y cells, and explore the effect and possible mecha- nism of AGEs on Alzheimer＇s disease（AD） the cell level. Methods Cultured SH-SY5Y ceils were randomly divided into four groups： the blank control group, the AGE-modified bovine serum albumin （AGEs-BSA） group, the AGEs- BSA ＋ anti-receptor for advanced glycation end products（RAGE） group and the BSA group. The MTT metabolic rate was employed to determine cells＇ growth and best concentration and time of the AGEs-BSA. Immunocytochemistry and ELISA were used to observe expressions of Aβ1-40 and Aβ1-42. Western blot was employed to examine changes of the amyloid precursor protein （ APP）, β- secretion enzymel （ BACE1 ） and presenilinl （ PSI ） in SH-SY5Y cells. Results There was no difference in APP, BACE1, PS-land Aβ between the blank control group and the BSA group（P 〉 0.05）. Immunocytochemistry and ELISA results indicated that expression of A13 in cells was significantly higher in AGEs-BSA and AGEs-BSA ＋ antiRAGE groups than in the BSA group （ P 〈 0.05 ）, and it was lower in the AGEs-BSA ＋ antiRAGE group than that in the AGEs-BSA group （ P 〈 0.05 ）. Western blot showed that APP, BACE1 and PSI levels in SH-SY5Y cells were elevated in AGEs-BSA and AGEs-BSA ＋ antiRAGE groups compared with the BSAgroup（ P 〈0.05 ）, and concentrations of them in the AGEs-BSA ＋ antiRAGE group were lower than those in the AGEs- BSA group（P 〈 0.05）. Conclusion AGEs-BSA promotes expression of APP, and it promotes expression of A[~ by up-regulating activities of BACE1 and PS1. The blocking combination of AGEs-BSA and its receptor（RAGE） reduces expressions of APP, BACE1, PSI and Aβ.