Aucubin Provides Cerebroprotection In A Mice Subarachnoid Hemorrhage Model And The Research Of Its Mechanism

Background:Subarachnoid hemorrhage(SAH)is an acute disease.The neurological damage after SAH is induced by early brain injury.Aucubin can provide cytoprotection in cirrhosis,epilepsy and diabetic encephalopathy.However,none of the previous studies has demonstrated its cerebroprotective effects after SAH.Therefore the aim of this study was to determine the protective effects and its possible mechanism of Aucubin in a mice SAH model.Methods:Male mice(20-25 g)were randomly assigned into the following groups:Sham group;SAH group;SAH Aucubin(20,40,80 mg/kg)groups.The SAH mice model was established using endovascular perforations.Mice in Aucubin groups were injected intraperitoneally with Aucubin solution at 30 minutes after SAH.Compound C,a specific AMP-activated protein kinase(AMPK)inhibitor,was injected 30 minutes before SAH.The mice were sacrificed at 24 hours after SAH and brain samples were subjected to western blot,cerebral edema evaluation,Nissl staining,immunofluorescence,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)and malondialdehyde(MDA)content testing.Results:Neurological dysfunction and brain edema were alleviated by Aucubin-treatment.Nuclear translocation of nuclear factor erythroid 2-related factor 2-antioxidant responsive element(Nrf2-ARE)path was activated by Aucubin-treatment,which was demonstrated by the increase of nuclear-Nrf2 the downstream proteins including quinine oxidoreductase 1(NQO-1)and heme oxygenase 1(HO-1).Additionally,SAH-induced anti-inflammatory and anti-oxidative responses after SAH was reduced by Aucubin,demonstrated by the lower levels of inducible nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2),as well as by higher levels of oxidative stress indicators such as glutathione peroxidase 1(GPx1),superoxide dismutase 3(SOD3)and MDA.SAH-induced apoptosis was reduced by Aucubin-treatment,demonstrated by increased levels of B-cell lymphoma 2(Bcl-2)and the decreased levels of Bcl-2-associated X protein(Bax)and cleaved-caspase 3,as well as by TUNEL assay.Inhibition of AMPK blocked the Aucubin-induced anti-inflammatory,antioxidant and antiapoptosis effects.Conclusion:Aucubin provided anti-inflammatory,antioxidative and antiapoptotic effects via the AMPK in the mice SAH model.