Abstract: 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 FPS-ZM1. 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 Aβ_1-40 and Aβ_1-42 of 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 Aβ_1-40 and Aβ_1-42 were 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.

Key words: Advanced glycation end products, RAGE inhibitor, Aβ, Alzheimer’s disease, β-secretase