[Total Astragalus saponins reduce astrocyte swelling and AQP4 expression following oxygen-glucose deprivation and reoxygenation by inhibiting the p38 pathway].

OBJECTIVES

To investigate the effect of total Astragalus saponins (AST) on astrocyte swelling induced by glucose-oxygen deprivation and reoxygenation (OGD/R) and its molecular mechanism.

METHODS

Primary astrocytes isolated from the brain of post-natal day 2 SD rats were treated with solvent vehicle, AST, or AST combined with U-46619 (a p38 activator) 24 h prior to and during exposure to OGD/R. The changes in cell volume and morphology were observed, and intracellular reactive oxygen species (ROS) levels and lactate dehydrogenase (LDH) activity were detected. The expression of aquaporin 4 (AQP4) on cell membrane was observed using immunofluorescence confocal microscopy, and Western blotting was performed to detect the changes in p38 signaling pathway phosphorylation levels and AQP4 expression level.

RESULTS

AST treatment significantly reduced OGD/R-induced increase in astrocyte volume, ROS levels and LDH release. The AST-treated cells also exhibited improved cell morphology, reduced aggregation of AQP4 on the cell membrane, and decreased p38 phosphorylation and AQP4 expression levels. The protective effects of AST against OGD/R-induced cell injuries were significantly attenuated by combined treatment of the cells with U-46619.

CONCLUSIONS

AST alleviate astrocyte swelling induced by OGD/R injury by inhibiting the activation of the p38 signaling pathway and AQP4 overexpression on the cell membrane.