Study On The Expression Of Nrf2 Signaling Pathway In Contused Brain Tissue After Human Brain Injury

Background and objective: Secondary brain injury,which occurs following traumatic brain injury(TBI)and has complex injured mechanisms,could further exacerbate brain injury.However,studies have shown that the development secondary brain injury could be inhibited via intervening one or more injured mechanisms.Therefore,it is the key point of treatment for patients with traumatic brain injury to prevent and reduce secondary brain injury.Accumulating evidence suggests that nuclear factor erythroid 2-related factor 2(Nrf2)signal pathway could be activated in experimental TBI models to alleviate secondary brain injury and play a critical role in neuroprotection by up-regulating the expression of hundreds of cytoprotective proteins.This study would apply the results of animal experiments to clinical practice to investigate the neuroprotection of Nrf2 signal pathway via detecting the expression of Nrf2 and Nrf2-regulated gene products in human injured brain tissue after TBI.Methods: 31 specimens of injured brain tissue obtained from patients who accepted emergency neurosurgeries for hematoma and contusion removal were divided into 3 groups according to the duration of TBI before surgery(A,?6h,n=12;B,6-24 h,n=12;C,>24 h,n=7).5 specimens of control brain tissue obtained from patients who accepted the excision of benign tumor on the skull base were used as control.Western bolt was performed to detect the expression of nuclear and cytoplasmic Nrf2 and Nrf2-regulated gene products,NAD(P)H quinine oxidoreductase 1(NQO-1)and Glutathione S-transferase(GST).Immunohistochemical staining was performed to exam the expression of NQO-1 and GST.Quantitative real-time PCR was used to analyze the mRNA levels of NQO-1 and GST-?1.Results: The nuclear level of Nrf2 increased,while the cytoplasmic level decreased significantly as the duration of TBI lengthened(P<0.05).The expression of NQO-1 and GST increased significantly after TBI as well(P<0.05).In addition,the mRNA levels of NQO-1 and GST-?1 increased significantly after TBI(P<0.05).Conclusion: Nrf2 signal pathway could be activated after TBI and up-regulate the expression of its gene products to confer neuroprotection.Nrf2 signal pathway could serve as a novel effective therapeutic target to develop new treatments for improving prognosis of patients after TBI.