This study aimed to investigate the role of
tanshinone IIA (TSO IIA) in astrocytic swelling caused by
ischemia-reperfusion-like injury in an in vitro model and the molecular mechanisms underlying this effect. Primary brain astrocytes were cultured under conditions of
glucose and
oxygen deprivation and reoxygenation (OGD/R). The study explored the effects of TSO IIA treatment on cell swelling and injury and the
protein levels of
aquaporin 4 (AQP4) in the plasma membrane. It then examined the involvement of the high-mobility group box
protein 1 (
HMGB1)/receptors for
advanced-glycation end products (RAGE)/
nuclear factor-kappa B (NF-κB)/
interleukin-6 (IL-6) pro-inflammatory axis in TSO IIA-mediated protection. The treatment with TSO IIA alleviated OGD/R-induced astrocytic swelling and the overclustering of
AQP4 protein in the plasma membrane. In addition, TSO IIA significantly reduced the overexpression of
HMGB1 and the high levels of the NF-κB
protein in the nucleus and of the
IL-6 protein in the cytoplasm and extracellular media induced by OGD/R. The combination of TSO IIA and recombinant
HMGB1 reversed these effects. The inhibition of the RAGE, the receptor of
HMGB1, induced results similar to those of TSO IIA. In addition, exogenous
IL-6 reversed TSO IIA-mediated effect on AQP4 overclustering and cell swelling. TSO IIA significantly reduced astrocyte swelling after OGD/R injury in vitro, via blocking the activation of the
HMGB1/RAGE/NF-κB/IL-6 pro-inflammatory axis and thereby decreasing the expression of AQP4 in the plasma membrane.