| Objective Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is activated after traumatic brain injury (TBI), and it plays an important protective role. The animal experimental studies have demonstrated that as a novel Nrf2 activator, tert-butylhydroquinone (tBHQ) can protect mice brain against TBI-induced inflammatory response and decrease secondary brain injury. The aim of this study was to take a further investigation of tBHQ on the protective role and its mechanism against inflammatory damage after TBI by experiments in vitro.Methods Primary neuronal cells were cultured from ICR fetal rats, when the cells matured, they were divided into three groups:(1):sham+vehicle group; (2):TBI+vehicle group; (3): TBI+tBHQ group (n=18 per group).24h after the cells got injured, we measured the content of Nrf2 in cytoplasm and nucleus by Western-Blot, Nrf2 and nuclear factor kappa B (NF-κB) binding activities by electrophoretic mobility shift assay (EMSA), the mRNA expression of the cytokines from Nrf2 signaling pathway like NAD(P)H:quinone oxidoreductase 1 (NQO1), Hemoxygense-1 (HO-1), Glutathione S-transferase (GST)、γ glutamylcysteine synthetase(Y GCS) by Real-time Polymerase Chain Reaction (PCR), the content of glutathione (GSH) and GSSG by chemiluminescence and the expression of reactive oxygen species (ROS) by fluorescence in the cell supernatant.Results The Nrf2 and its cytokines like NQO1、HO-1、GST、γ GCS were significantly activated following TBI and could be induced when treated with tBHQ (P<0.05); the inflammatory-related factor NF-κB and the content of ROS in the cell supernatant were significantly up-regulated following TBI (P<0.05) and could be suppressed when treated with tBHQ (P<0.05).Conclusion TBHQ could attenuate the cerebral inflammatory response and played a protective role after TBI. The propable mechanism might be through the activation of Nrf2 signalling pathways and then maintain the redox status, thus inhibiting NF-κB activation. |
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