Targeting AGEs-RAGE pathway inhibits inflammation and presents neuroprotective effect against hepatic ischemia-reperfusion induced hippocampus damage - 27/02/22
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Highlights |
• | HIR increased the hippocampal damage and enhanced its neuron apoptosis. |
• | AGEs-RAGE signaling, its downstream proteins, and inflammation were activated by HIR. |
• | FPS-ZM1 attenuated hippocampal damage, inhibited neuron apoptosis, inhibited inflammation. |
Abstract |
Background |
The present study aimed to investigate the role of AGEs-RAGE signaling and its potential as a treatment target in hepatic ischemia-reperfusion (HIR)-induced hippocampus damage.
Methods |
HIR operation was conducted in mice, followed by collection of hippocampus tissue at 1 day, 3 days and 7 days. Additionally, low dose, moderate dose and high dose FPS-ZM1 (RAGE inhibitor) was intraperitoneally injected into HIR mice. Besides, sham operation was conduced in mice which served as control.
Results |
HIR increased the hippocampal damage and enhanced its neuron apoptosis within 3 days, which recovered to some extent from day 3 to day 7 post operation. Meanwhile, the expressions of AGEs, RAGE, the downstream proteins in AGEs-RAGE signaling pathway (including PI3K, pAKT, pNKκB p65 and pERK1/2), and the inflammatory cytokines (including IL-1β, IL-6, TNF-α) were increased within 3 days, but were reduced from day 3 to day 7 post operation by HIR. Notably, moderate and high dose of FPS-ZM1 attenuated hippocampal damage, inhibited its neuron apoptosis, inactivated AGEs-RAGE signaling, and suppressed the expressions of inflammatory cytokines (including IL-1β, IL-6, TNF-α); but lose dose of FPS-ZM1 failed to achieve these effects.
Conclusions |
Targeting AGEs-RAGE pathway inhibits inflammation and presents neuroprotective effect against HIR-induced hippocampus damage.
El texto completo de este artículo está disponible en PDF.Keywords : AGEs-RAGE signaling, Hepatic ischemia-reperfusion, FPS-ZM1, Hippocampal damage, Neuronal cell
Abbreviations : HIR, ROS, AGEs, RAGE, h, HE, TUNEL, NIH, SD
Esquema
Vol 46 - N° 2
Artículo 101792- février 2022 Regresar al número
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Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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