关键词: 阿尔茨海默病；糖基化终末产物；β-淀粉样蛋白

Abstract:

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 mechanism of AGEs on Alzheimer′s disease(AD) the cell level. MethodsCultured SH-SY5Y cells 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 enzyme1(BACE1) and presenilin1(PS1) in SH-SY5Y cells. Results     There was no difference in APP, BACE1, PS-1and Aβ between the blank control group and the BSA group(P>0.05). Immunocytochemistry and ELISA results indicated that expression of Aβ 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 PS1 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 Aβ by up-regulating activities of BACE1 and PS1. The blocking combination of AGEs-BSA and its receptor(RAGE) reduces expressions of APP, BACE1, PS1 and Aβ.

Key words: Alzheimer′s disease; Andadvanced glycation end products; β-amyloid protein