RESUMO
Objective To study the clinical significance of the injury and functional change of hypothalamic-pituitary-adrenal (HPA) axis after acute severe traumatic brain injury (TBI) in the rats.Methods A total of 60 adult healthy male Spraque-Dawley rats were randomly (random number) divided into 3 groups (n =20 in each group):sham operation group,model group and treatment group.The TBI models of rats were established by Feeney' s method.A low dose of dexamethasone (0.6 mg/kg) was injected into the abdominal cavity 20 minutes,24 hours and 48 hours after injury in treatment group,while rats of sham operation group and model group received equal volume of normal saline instead.All the rats were injected 1 μg adrenocorticotropic hormone (ACTH) into the abdominal cavity.The related parameters were detected at four time points,3 hours,12 hours,24 hours and 72 hours after cerebral contusion.The plasma corticosterone (CORT) and ACTH levels were measured by chemiluminescence.The hypothalamic,pituitary and adrenal of the rats were taken out for observing interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression detecting by immunohistochemical techniques at 72nd hour after TBI.One-way ANOVA and SNK-q test were used to analyze the results with SPSS 17.0 software package.Results The levels of ACTH and CORT on 3rd hour of model group raised remarkably compared with that of sham operation group,then they reduced gradually.The levels of CORT were lower than that of sham operation group at every time points after ACTH stimulation test (P ＜0.05 or P ＜0.01).The levels of CORT at all time points of treatment group were changed remarkably compared with that of model group.However,the ACTH levels of treatment group on 24 h increased slightly than that of model group.And the tendency of them was similar to model group (P ＜ 0.05 or P ＜ 0.01).The number of the hypothalamus and pituitary cells which express IL-6 and TNF-α in model group was more significantly increased when compared with that in sham operation group (P ＜ 0.01),while the number of this kind of cell in treatment group was significantly decreased than that in model group (P ＜ 0.01).The number of the adrenal cortex cells which express IL-6 in treatment group was more significantly decreased when compared with that in model group (P＜ 0.01),while the number of this kind of cell in model group was significantly increased than that in sham operation group (P ＜ 0.01).However,there was no significant difference of the TNF-α between all the groups (P ＞ 0.05).Conclusions Functional change of adrenal occurs early in the severe acute traumatic brain injury rats,and the response of adrenal to ACTH decreased as time goes by.Low-dose,short-course dexamethasone can delay the pathological changes,reduce the inflammatory response of HPA axis and increase the sensitivity of adrenal response to ACTH.
