Protective Effect and Mechanism of Platycodonopsis Saponin D on Cer-ebral Ischemia/Reperfusion-Induced Blood-Brain Barrier on PI3K/AKT/mTOR Pathway Based
To investigate the mechanism and the protective effect of Platycodin D(PLD)on cerebral ischemia/reperfusion-induced blood-brain barrier via PI3K/AKT/mTOR pathway in this study.Middle cerebral artery occlusion model was constructed in Sprague-Dawley dia-betic rats.Animal experiments were divided into sham group,HIR group,PLD group,3-MA group(3-methyladenine,3-methyladenine)and PLD+3-MA group.Nerve function deficit score,cerebral water content,cerebral infarction volume and blood-brain barrier permeability were analyzed in each group.Ultrastructural changes and autophagy of blood-brain barrier were observed by transmission electron micro-scopy.Western blot analysis of tight junction(tight junction,the expression of autophagy associated proteins(Beclin-1,LC3B and p62)and PI3K/AKT/mTOR pathway related proteins were analyzed by immunofluorescence staining of TJ proteins(ZO-1,claudin-5 and occludin)and western blot.Treatment with PLD and autophagy inhibitor 3-MA significantly decreased infarct volume,brain water content and evans blue leakage,increased the expression of TJ protein and decreased the expression of autophagy related proteins(P＜0.05).In addition,PLD increased the phosphorylation levels of PI3K,AKT and mTOR.PLD prevents blood-brain barrier injury after cerebral ischemia-reper-fusion injury in hyperglycemia by inhibiting autophagy,which may be achieved by regulating PI3K/AKT/mTOR signaling pathway.
platycodon DPI3K/AKT/mTOR pathwaycerebral ischemia and reperfusionblood brain barrier
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