【摘 要】
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Sepsis is life-threatening organ dysfunction due to dysregulated systemic inflammatory and immune response to infection,often leading to cognitive impairments.Growing evidence shows that artemisinin,an antimalarial drug,possesses potent anti-inflammatory
【机 构】
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Department of Emergency,The Second Affiliated Hospital of Guangzhou Medical University,Guangzhou 510
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Sepsis is life-threatening organ dysfunction due to dysregulated systemic inflammatory and immune response to infection,often leading to cognitive impairments.Growing evidence shows that artemisinin,an antimalarial drug,possesses potent anti-inflammatory and immunoregulatory activities.In this study we investigated whether artemisinin exerted protective effect against neurocognitive deficits associated with sepsis and explored the underlying mechanisms.Mice were injected with LPS(750μg·kg-1·d-1,ip,for 7 days)to establish an animal model of sepsis.Artemisinin(30mg.kg-1·d-1,ip)was administered starting 4 days prior LPS injection and lasting to the end of LPS injection.We showed that artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests,attenuated neuronal damage and microglial activation in the hippocampus.In BV2 microglial cells treated with LPS(100ng/mL),pre-application of artemisinin(40μM)significantly reduced the production of proinflammatory cytokines(i.e.,TNF-α,IL-6)and suppressed microglial migration.Furthermore,we revealed that artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway;knockdown of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin in BV2 microglial cells.In conclusion,atemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment,and its effect is probably mediated by activation of the AMPKα1 signaling pathway in microglia.
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