The Basic Research Of Anti-apoptotic Mechanism Of The Nrf2 Signal Pathway After Traumatic Brain Injury

Objective Apoptosis plays an important role in the pathogenesis of secondary brain injury after traumatic brain injury(TBI).Our previous studies have shown that Nuclear factor erythroid 2-related factor 2(Nrf2)is a key transcription factor that plays a crucial role in cytoprotection after TBI,such as anti-inflammation,anti-apoptosis and so on.Notch1 pathway has been demonstrated that also plays vital roles in controlling cell proliferation,differentiation and apoptosis.So the aim of this study is to investigate the relationship between the Nrf2 and notch signaling.Methods Wild-type Nrf2(+/+)and Nrf2(-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury.Notch pathway signal related proteins Notch 1,Hes-1 and NICD were detected using western blotting.At last the apoptosis related proteins like Bcl-2,Bax and caspase-3 detected using western blotting and apoptotic neuron death were detected by TUNEL..Results The down-regulating of Nrf2 pathway can inhibit the activation of Notch 1 signal pathway and lead to more neuron apoptotic death after TBI.Conclusion We found that Notch 1 signaling was down-regulated in Nrf2(-/-)-deficient group,and the quantity of caspase-3 and Bax was higher in this group.The results suggest that Nrf2 plays a significant protective role in up-regulating the notch expression and inhibit the apoptosis.