Neuroprotection of early and short-time applying berberine in the acute phase of cerebral ischemia:Up-regulated pAkt,pGSK and pCREB,down-regulated NF-κB expression,ameliorated BBB permeability

【作者】 张晓林； 张祥建； 王超慧； 李艳华； 董立鹏；

【Author】 Xiaolin Zhang;Xiangjian Zhang;Chaohui Wang;Yanhua Li;Lipeng Dong;

【机构】 河北医科大学第二医院神经内科；

【摘要】 Background and object;Berberine(BBR) has gained attention for its vast beneficial biological effects through immunomodulation,anti-inflammatory and anti-apoptosis properties.Inflammatory and apoptosis damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment.The aim of this study was to explore BBR’s effect in ischemic injury and the role of the Akt/GSK(glycogen synthase kinase) signaling cascade in mediating the anti-apoptosis and anti-inflammatory effects in the rat brain of permanent middle cerebral artery occlusion(pMCAO).Methods:Male SpragueDawley rats were subjected to pMCAO and randomly assigned into four groups:Sham(sham-operated)group,pMCAO(Pmcao + 0.9%saline) group,BBR-L(pMCAO + BBR 10 mg/kg) and BBR-H(pMCAO + BBR40 mg/kg) group.BBR was administered immediately after pMCAO and the neuroprotection was detected.Phospho-Akt(pAkt),phospho-glycogen synthase kinase 3-B(pGSK3B),phosphocAMPresponse element binding protein(pCREB),nuclear factor-kappa B(NF-kB) and claudin-5 in ischemic cerebral cortex were detected by immunohistochemistry,reverse transcriptionpolymerase chain reaction and western blotting.Results;Compared with pMCAO group,BBR dramatically lessened neurological deficits scores,brain water contents and infarct sizes,upregulated the expression of pAkt,pGSK3 B,pCREB and claudin-5,and decreased the nuclear accumulation of NF-kB(P < 0.05) in ischemic brain.Conclusion;The results showed that BBR reduced ischemic brain injury after pMACO,and this effectmay be via the increasing the activation of Akt/GSK signaling and claudin-5,and decreasing NF-kB expression.更多还原

【Abstract】 Background and object;Berberine(BBR) has gained attention for its vast beneficial biological effects through immunomodulation,anti-inflammatory and anti-apoptosis properties.Inflammatory and apoptosis damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment.The aim of this study was to explore BBR’s effect in ischemic injury and the role of the Akt/GSK(glycogen synthase kinase) signaling cascade in mediating the anti-apoptosis and anti-inflammatory effects in the rat brain of permanent middle cerebral artery occlusion(pMCAO).Methods:Male SpragueDawley rats were subjected to pMCAO and randomly assigned into four groups:Sham(sham-operated)group,pMCAO(Pmcao + 0.9%saline) group,BBR-L(pMCAO + BBR 10 mg/kg) and BBR-H(pMCAO + BBR40 mg/kg) group.BBR was administered immediately after pMCAO and the neuroprotection was detected.Phospho-Akt(pAkt),phospho-glycogen synthase kinase 3-B(pGSK3B),phosphocAMPresponse element binding protein(pCREB),nuclear factor-kappa B(NF-kB) and claudin-5 in ischemic cerebral cortex were detected by immunohistochemistry,reverse transcriptionpolymerase chain reaction and western blotting.Results;Compared with pMCAO group,BBR dramatically lessened neurological deficits scores,brain water contents and infarct sizes,upregulated the expression of pAkt,pGSK3 B,pCREB and claudin-5,and decreased the nuclear accumulation of NF-kB(P < 0.05) in ischemic brain.Conclusion;The results showed that BBR reduced ischemic brain injury after pMACO,and this effectmay be via the increasing the activation of Akt/GSK signaling and claudin-5,and decreasing NF-kB expression.更多还原