The Protective Effect Of HIF-1? In The Traumatic Brain Injury And Its Related Molecular Mechanism

Objective With the rapid development and progress of our modern society these years,numerous traumatic brain injury(TBI)with gradually increasing incidence,morbidity,mortality was caused by the by traffic and industrial accidents,natural disasters,war and other causes,especially severe accident,and the use of weapons of mass destruction which resulted in noderate or severe TBI and the fatal damage for the patients,families and society.Therefore,the exploration about the pathogenesis,effective interventions,as well as the therapy for the TBI were paid more attention in the field of trauma,and neurological medicine.Hypoxia-inducible factor-1?(HIF-1)which is closely related to a variety of pathological changes of TBI plays an importantly maintaining and promoting role in the pathophysiological process such as adaptation,survival,apoptosis,neurovascular repair and regeneration within the environment of ischemia and hypoxia after TBI.In view of these former research,we intend to observe whether HIF-1? takes effects to the inflammation and angiogenesis promotion,and detect the probably protective effect of HIF-1? in the process of TBI through regulating the molecular of HIF-1? in our study.Methods Establishing the Wistar rat model of TBI with fluid percussion impact machine and the animals were divided to four groups including sham group,TBI group,HIF-1? silence group,and control plasmid group,and the time point was set on day 3? day 7?and day 14 after the percussion injury(the three periods of acute,subacute,chronic phase):(1)Evaluating the dynamic changes of neurological function by mNSS neurological evaluation scale.(2)observing the injured area and the morphology in the injured zone by HE staining;(3)testing the expression of HIF-1? and vWF in the brain tissue by Western Blot;(4)detecting the expression of VEGF,TNF-?,IL-6 and NF-?B in the brain tissue by ELISA assay;(5)observing the protective effect of HIF-1? in the TBI process with statistical analysis,and detecting its molecular mechanism associated with inflammation and angiogenesis.Results(1)The expression of HIF-1? and vWF significantly decreased in the HIF-1? silence group at the three stages after TBI(P<0.05,P<0.05,P<0.05),which suggested that the HIF-1? silence inhibited the angiogenesis during the recovery of TBI.(2)The level of HIF-1? in TBI group increased at the 3rd day after hydraulic perfusion compared with the sham group and HIF-1? group(P <0.05,P <0.05),and it maintained the increasing tendency at the 7th and 14 th day after injury(7th day P <0.05,P <0.05,14 th day P <0.05,P <0.05).(3)The brain edema recovered obviously in the TBI group compared with the HIF-1? silence group at 3rd,7th,14 th day(P <0.05,P <0.05,P <0.05),and the neurological function gradually improved in TBI group compared with the HIF-1? silence group(P <0.05,P <0.05).(4)The VEGF activating level significantly decreased in HIF-1? silence group compared with the TBI group at 3rd,7th,14 th day(P <0.05,P <0.05,P <0.05),and the MMP-9 activating level reduced a little at the 3rd day(P>0.05)while decreased obviously at the 7th and 14 th day(P<0.05,P<0.05)(5)The IL-6 and TNF-? level and the activation of NF-?B in the TBI group reduced significantly compared with the HIF-1? silence group(P<0.05,P<0.05,P<0.05,respectively).Conclusion HIF-1? could decrease the brain edema,protect and modify the neurological function after TBI via dual effects of inhibiting inflammation and promoting angiogenesis.