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Targeting AGEs-RAGE pathway inhibits inflammation and presents neuroprotective effect against hepatic
1Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.
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.
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