Regulation Of Pituitary AQP4and ACTH By Hyperbaric Oxygen Therapy After Injury By Explosion In Rabbit

Background With the high-technology weapons used in local regional war, theproportion of blast injury goes up, has become to the key focus of the military medicalresearch at home and abroad. The disability and death rates are quite high after brainexplosive injury because of the complications, especially the internal environmenthomeostasis disruption which caused by neuroendocrine dysfunction in stress reaction.Recently, researchers did lots of extensively studies, but mainly concentrated in thebrain edema formation after brain injury. Some studies have found that AQP4expression in pituitary tissue as a water permeability of the membrane transporterprotein, which is sensitive to changes in intracellular and extracellular osmotic pressure,whether it involved in hormone secretion of pituitary gland cells need to be furtherinvestigated. Although there has certain speculation, no direct and clear evidenceindicates the relationship between them. The efficacy of hyperbaric oxygen treatment ofbrain injury is positive, and its inhibition of AQP4expression in the treatment ofcerebral edema has been reported. My study intends to explore the relationship betweenregulation of pituitary AQP4and ACTH(Adrenocorticotropic Hormone) after brainexplosive injury using the brain explosion rabbit model, and further observe thisrelationship changes after hyperbaric oxygen therapy.Objective①Eestablishment of the brain explosive injury model in rabbits; Research ofAQP4and ACTH changes in pituitary and explore the relationship of them after brainexplosive injury.②Observe the regulation of AQP4and ACTH after Hyperbaricoxygen therapy, providing a theoretical basis for hyperbaric oxygen treatment of pituitary dysfunction in acute traumatic brain injury.Method150New Zealand rabbits (male and female unlimited) were randomly dividedinto3groups: non-treatment group(70), treatment group(70) and control group(10).Blast injury model of rabbit brain was took600mg TNT paper detonators suspensionand detonation point keep vertical distance6.5cm on the top of the rabbit brain. In thetreatment group and non-treatment group were detonated, and the control group werenot implemented detonated. The treatment group rabbits were executed early hyperbaricoxygen therap, treatment group and the non-treatment group animals were randomlysacrificed at corresponding time points (1h,6h,12h,24h,72h,7d,14d) after injury,each group of10animals. The control group and the treatment group by dry-wetmethod to measure the water content of the proportion of pituitary gland.Immunohistochemical staining to detect the AQP4and ACTH expression of rabbitpituitary in the three groups, and then use of double immunohistochemical stainingmethod to detect the coexisting conditions among them, and perform the correspondingstatistics analysis.Result①Injured animals wereawake in3-5h after injury, listlessness and poorappetite after wake up.9rabbits occurred epilepsy and3rabbits got paralysis of limbs,5rabbit died on the third day after injury because of inability eating. Give to supplementmade model, and finally into the result analysis experiment rabbits are150.②TheAQP4expression of rabbit pituitary were increased with the prolongation of the timeafter brain blast injury, peaked at72h, start down after7d,14d still significantexpression(P <0.05). The AQP4expression of rabbit pituitary which treated byHyperbaric oxygen compared with non-treatment group reduced6hours after injury,the difference was significant significance (P <0.05), expressed and tended to be normalin14days after injury (P>0.05). Pituitary moisture content and AQP4consistent expression changes, were positively correlated(r=0.886, P <0.05), The expression ofACTH in non-treatment group were began increase in1h after injury,6h,12h,24h wereincreased, peaked at3d,7d started to cut (at each time point compared with the controlgroup, P <0.05).In the same time point treatment group compared with the controlgroup to be express higher, but compared with the non-treatment group loweredsignificantly (P <0.05),there were no significant difference among the three groups in14d(P>0.05，the ACTH expression of4animals in non-treatment group were lowerthan in the control group the lowest value). There were positively correlated throughcorrelation analysis of AQP4and ACTH expression changes in non-treatment group (r=0.959, P <0.001).Conclusion①Estiblishement of the brain explosive injury model.②The expressionof AQP4and ACTH in the pituitary gland was positively correlated and time dependentafter rabbit brain explosive injury, suggested that the pituitary gland AQP4may beinvolved in ACTH secretion.③Hyperbaric oxygen therapy can reduce the secretion ofACTH through inhibiting the expression of the AQP4, this may be one of themechanisms of pituitary dysfunction in the treatment of brain injury.