The Study On The Mechanism Of The Benzodiazepine Receptor's Function In Brain Radiation Injury

ObjectiveThe radiation injury is one of the serious complications following the radiation therapy. This research selected diazepam as the benzodiazepine receptor agitator to protect the brain radiation injury and flumazenil as agonist. The experiments investigated the benzodiazepine receptor's role under the acute brain radiation injury in the early stage on tissue and protein level.MethodsA model of whole brain radiation injury in wakefulness as Wang chen reported was established in order to eliminate the side effects from the anesthesia agents.30Gy was selected as irradiation dosages. Experiment rats were divided into such groups with the randomly, group A: the group irradiated with no-medicine used; group B: the group irradiated with diazepam used; group C: the group with no- irradiated and diazepam used; group D: the group irradiated with flumazenil used; group E: the group with no irradiated and flumazenil used; group F: the group irradiated with diazepam and flumazenil used. The observation was done before radiation and 6 hours, 1 day, 1 week, 1 month after irradiation. 1 , The effect of the benzodiazepine receptor to the free radical after irradiated: Detected the effect of diazepam and flumazenil to the vigorof the superoxide dismutase ( SOD ) and the contents of malondialdehyde ( MDA ) after the brain tissue homogenate. 2, The effect of the benzodiazepine receptor on the blood brain barrier ( BBB ) after irradiated :(1) Protein level: Immunohistochemical staining was used to analysis the effect of diazepam and flumazenil on the expression of vascular endothelial growth factor ( VEGF) in the brain tissue.(2) Tissue level: Examining the content of the Evan's blue (EB) inside brain tissue was used to analysis the effect of diazepam and flumazenil on the BBB permeability quantitatively.3 , The effect of the benzodiazepine receptor on the neuron in the hippocampus region after irradiated: Observed to the changes of the pathomorphology with the Hematoxylir-eosin (HE) staining, and the effect of diazepam and flumazenil to the changes of influence degree.Results1, Compared with the group irradiated with no-medicine used, The group of irradiated with diazepam showed the increasing of SOD at 6 hours , 1 day after irradiation, and decreasing of the MDA contents at 6 hours, 1 month after irradiation.2, Compared with the group irradiated with no-medicine used, The group of irradiated with diazepam showed the decreasing BBB permeability from the result of EB examine at 6 hours, 1 week, 1 month after irradiation. In addition, immunohistoohemical staining confirmed that diazepam in this group could decrease VEGF expression at 6 hoursafter irradiated. 3, Compared with the group irradiated with no-medicine used, The groupof irradiated with diazepam showed the lighten the neuron injury in the hippocampus region after irradiated.4, The role of diazepam could be alleviated by flumazenil in some period. It has no significantly difference between the group irradiated with no-medicine used and the group irradiated with flumazenil used; the group with no irradiated and flumazenil used and the group with no-irradiated and diazepam used.ConclusionDiazepam had protection action in some degree to the brain irradiation injury and flumazenil had not protection action and the role of diazepam could be alleviated by flumazenil in some period in our observation. We could infer the benzodiazepine receptor play a protective role in the brain radiation injury.