ABSTRACT
Objective To explore the effect of astragaloside IV on the damaged blood-brain barrier (BBB) in vitro model induced by amyloid-beta protein (Aβ1-42) and the underlying mechanism. Methods Firstly, the non-contact co-culture blood-brain barrier (BBB) model was established by Aβ1-42-induced mouse brain microvascular endothelial cell (bEnd.3) and primary rat astrocyte (As). Then the mice were divided into four groups: control, model (Aβ1-42 30 μmol/L), astragaloside IV low and high dose groups (Aβ1-42 30 μmol/L with Astragaloside IV 50 and 200 μmol/L). The effect of astragaloside IV on the vitality of bEnd.3 induced by Aβ1-42 was detected by methyl thiazolyl tetrazolium (MTT) assay. The permeability of BBB in vitro was determined by detecting the quantity of fluorescein sodium through BBB in various groups. In order to explore the mechanism of its protection, the apoptosis related proteins Caspase-3, cleaved Caspase-3 and tight junction proteins ZO-1, Claudin-5 and Occludin were detected by Western blotting. Results Compared with model group, the astragaloside IV groups improved the activity of bEnd.3 cells significantly (P < 0.001). The protective effect was positively correlated with the concentration of astragaloside IV. Astragaloside IV with low and high dose decreased the permeability of BBB model in vitro (P < 0.001). According to the results of Western blotting, the ratio of cleaved Caspase-3/Caspase-3 was significantly declined, and the expression levels of ZO-1, Claudin-5 and Occludin were significantly increased in astragaloside IV groups (P < 0.05). Conclusion Astragaloside IV may play a BBB protective role by inhibiting the apoptosis of bEnd.3 cells induced by fibrous Aβ1-42 and increasing the expression of tight junction proteins.