| Objective: Traumatic Brain Injury(TBI)has become the leading cause of death and disability among young and middle-aged people all over the world.The main pathological processes after TBI include primary brain injury and secondary brain injury,and the secondary injury is a series of cellular and biochemical cascade occurs after primary injury,including inflammatory reaction,free radical damage,excitotoxicity,edema,overload of calcium,mitochondrial damage and a series of pathological process,and lead to cell dysfunction,cerebral edema,increased intracranial pressure,damage of brain regulation function,and ultimately aggravate brain damage and prognosis.Study shows that high mobility group 1(HMGB1)protein,as a proinflammatory mediators,has a central role in the inflammatory response to secondary brain injury.Traumatic brain injury combined with limb bone fractures is a common type of TBI complex injury in our clinical work,and these patients tend to be more severe than patients with simple TBI,the prognosis is worse.However,the study on the effect of limb bone fracture on the recovery of neurological function in patients with TBI and the role of HMGB1 in it is still blank.Therefore,the purpose of this study was to investigate the effects of limb fracture on the recovery of neurological function and prognosis in patients with TBI,and the role of HMGB1 in serum.Methods:1 Animal Experiment In this experiment,192 male C57 BL / 6 mice(12~14 weeks old,28~32g)were divided into control group,TBI group,TBI+BF group and TBI+BF+HMGB1 antibody group(all n = 48).After the model was made,the venous blood of the mice was extracted immediately,and then the serum samples were collected after centrifugation and stored in the refrigerator at-80 ?.Two days later,8 mice of each group were randomly selected,extracting venous blood and the serum samples were obtained at-80?.Then the neurological deficit score(NSS),Adhesive removal test,Corner test were proceeded.Test results were record and put back the mice to the cages.24 mice were selected from each group.Among them,8 were for brain water content test,8 were for inflammatory cytokines gene expression level tests by real-time polymerase chain reaction(RT-PCR),another 8 were fore detection of brain lesions volume.After 4 days of feeding,the serum samples of the mice in the four groups were collected and the mice were tested with the same method as the second day.The serum HMGB1 levels were measured by enzyme linked immunosorbent assay(ELISA).2 Clinical Experiment Forty-one individuals met the criteria for inclusion,and were divided into two groups: TBI group and TBI+BF group.GCS scores were recorded on admission,and the HMGB1 levels in the blood serum of the two groups were measured on the 1st,3rd,5th,and 7th day after injury.Ten health persons from examination center were assigned to control group.All patients were followed up for 6 months,and the GOS scores at the sixth month of injury were recorded.Results:1 The results of NSS score,adhesive removal test,corner test in both TBI group and TBI+BF group were worse than the control group on day 2 and 4(P<0.05).There was no statistical difference between TBI group and TBI+BF group in the NSS test on day 2,while the TBI+BF group was worse than TBI group on day 4(P < 0.01).The results of TBI+BF group in adhesive removal test were worse than TBI group on day 2 and 4(Day 2:P < 0.05,Day 4:P <0.05).There were no significant difference between TBI group and TBI+BF group in the Corner test on day 2,but the TBI+BF group turned more often to the left turn than the TBI group(P < 0.05).2 The injury and infarct volume: The volume in both TBI group and TBI+BF group are bigger than the control group on day 2 and 4(P<0.01).There was no significant difference between the two groups on day 2(P>0.05),the volume of TBI+BF group was significantly larger than the TBI group on the fourth day(P < 0.05).The brain water content: The content of both TBI group and TBI+BF group were higher than the control group on day 2 and 4(P < 0.05),no significant difference were found between TBI group and TBI + BF group on day 2(P > 0.05),but the TBI + BF group had a higher content than the TBI group on day 4(P < 0.05).3 The expression levels of TNF-?,IL-1? and IL-6 gene were higher in both TBI group and TBI+BF group than control group on day 2 and 4(P <0.01).The expression levels of TNF-? and IL-1? gene have no difference between TBI group and TBI + BF group on day 2(P > 0.05),but the expression level of IL-6 was higher in TBI + BF group than TBI group(P <0.05).On the forth day,the expression the levels of TNF-?,IL-1? and IL-6gene in TBI+BF group were higher than TBI group(TNF-?,IL-1?:P < 0.05;IL-6:P < 0.01).4 The serum HMGB1 levels: The levels were low and were the same at beginning among the three groups.The levels were significantly increased in TBI group and TBI + BF group and higher than control group on the second day(P < 0.01),and levels of TBI + BF group were higher than TBI group(P < 0.05).The level of HMGB1 in group TBI remained stable after 2 days of TBI,while the level of HMGB1 in TBI + BF group was higher than that in TBI group(P < 0.05).5 Compared with the TBI+BF group,on day 2 and 4,the TBI+BF+anti-HMGB1 antibody group got lower results in these tests: the percentage of injury and infarct brain tissue volume,brain water content,NSS score,and the frequency to turn left in corner test(P < 0.05).These results suggest that anti-HMGB1 antibody can reduce the brain injury.6 In clinical experiment,there was no significant difference in the GCS score between the TBI group and the TBI+BF group on admission(P < 0.05).The serum HMGB1 levels in the experimental group were higher than those in the control group(P < 0.01).The TBI group had lower serum HMGB1 levels than TBI+BF group on day 3,5 and 7(P<0.05),while had the same level on the first day(P > 0.05),indicating that serum HMGB1 level of TBI+BF group rose faster than TBI group.7 The GOS score of the TBI group was higher than that of the TBI+BF group at 6 months after injury(P <0.05),and the serum HMGB1 level of the patients in the group was negatively correlated with the GOS score(r=-0.619,P < 0.01).Conclusions:1 Both mice and human TBI could increase the blood HMGB1 level.2 HMGB1 is a late inflammatory factor,which increases gradually in the early stage of human and mouse TBI.3 TBI mice or patients with limb fractures can aggravate the inflammatory response of the brain by HMGB1,and further aggravate the secondary brain injury.4 The secondary brain injury can be reduced by decreasing the blood HMGB1 level of TBI mice with BF. |
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