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The Protective Effect And Mechanism Of Astilbin In Cerebral Ischemia Reperfusion Injury

Posted on:2021-04-20Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiFull Text:PDF
GTID:2404330605955389Subject:Surgery
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Stroke has become the second leading cause of death after ischemic heart disease.Ischemic stroke is the most common type of stroke.In the pathogenesis of ischemic stroke,cerebral injury not only occurred when blood flow was blocked,more s evere injury called cerebral ischemia-reperfusion injury may also occur after recanalization.As the main effective component of traditional Chinese medicine Rhizoma Smilacis glabrae,Astilbin has extensive biological activities,like inhibition of oxidative stress,anti-inflammation,anti-apoptosis and so on.Thus,Astilbin might be developed as a therapy agent for ischaemic strokeObjective The purpose of this study was to investigate the neuroprotective effects of Astilbin after cerebral ischaemia reperfusion(I/R)injuryMethods The PC 12 cells oxygen and glucose deprivation(OGD)model was used to simulate cerebral I/R injury in vitro.Cell viability was measured via CCK-8 and LDH release assays.Cell apoptosis was measured via Hoechst 33258 staining and Annexin V-FITC flow cytometry assays.ROS was detected via flow cytometry assay.The protein and inflammatory factors expression levels were determined by Western Blotting and ELISA.The middle cerebral artery occlusion(MCAO)model was used to simulate cerebral I/R injury in vivo.Cerebral ischaemic volume was measured by TTC staining.The Zea-Longa score,rota-rod test,and foot-fault test were used to evaluate behavioural changes and neurological deficits in ratsResults Astilbin significantly enhanced cell viability and decreased LDH release after OGD treatment in vitro.Astilbin effectively curbed cell apoptosis induced by OGD via inhibiting the activation of Caspase-3,decreasing the ratio of Bax/Bcl-2 and FADD Astilbin also inhibited OGD-induced inflammation by suppressing ROS-NLRP3 inflammasome axis activation.Further results revealed that Astilbin could regulate the MAPK pathway and activate the PI3K/AKT pathway.Finally,Astilbin significantly reduced the cerebral infarction volume and relieved neurological deficits in rats in vivoConclusion Astilbin could defend against cerebral I/R injury by inhibiting apoptosis and inflammation via suppressing the MAPK pathway and activating the AKT pathway.
Keywords/Search Tags:Astilbin, cerebral I/R injury, Apoptosis, NLRP3 inflammasome
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