Effect Of BACE-1and Beta-Amyloid On Hypothermia After Trauma Brain Injury In Rats

[Abstract] obj ective To investigate effect of BACE-1and beta-Amyloid Acting on the P-amyloid protein precursor on mild hypothermia after trauma brain injury(TBI) in rats.Methods A total of30male Wistar rats were randomly and equally divided into control group which underwent the same procedure without TBI, TBI with hypothermia ((32.0±0.5)℃) group and TBI with normothermia ((37.0±0.5)℃) group, each n=10, which treated with mild hypothermia or normothermia for6hours. The TBI rat model was established with a fluid percussion device.The behavior scales of nerve function were estimated, then the experimental animals were executed and hippocampus were saved Completed the behavior scales of nerve function. A part of rat hippocampus rapidly put in liquid nitrogen and translate to-70℃to save, a part of the rats brain was fixed in4%paraformaldehyde solution. The rats brain tissue which was fixed in4%paraformaldehyde solution was randomly selected to make paraffin section to observe the change of histopathology of the rats hippocampus tissues by hematoxylin and eosin (HE). The level of APP、 Aβ、BACE-1mRNA in the hippocampus was examined by reverse transcription-polymerase chanin reaction(RT-PCR), and protein expression of APP、 Aβ、BACE-1were analyzed by immunofluorescence and Western blotting, respectively.Results Compared with controls, the TBI normothermia group of neural function behavior score was reduced significantly (26.08±1.23vs.35.00±0.00, P<0.05), the number of survival neurons of hippocampus was decreased, the number of positive neurons of APP、 Aβ、 BACE-1in the hypothermia group was increased, and mRNA and related protein of APP、BACE-1increased obviously (APP mRNA:1.49±0.12vs.0.71±0.08, BACE-1mRNA:1.54±0.06vs.0.30±0.03and APP protein:1.78±0.03vs.0.76±0.02, Aβ protein:1.32±0.24vs.0.09±0.00, BACE-1protein:1.52±0.04vs.0.12±0.03all P<0.05). Compared with the TBI normothermia group, the neural function behavior score was improved significantly (32.29±1.31vs.26.08±1.23), the number of survival neurons of hippocampus was increased, and the number of positive neurons of、 Aβ、 BACE-1was increased tread with mild hypothermia. Hypothermia group showed lower expression of APP、 BACE-1and β-amyloid protein (Aβ) compared with normothermia group (APPmRNA:0.71±0.08vs.1.49±0.12, BACE-1mRNA:0.51±0.04vs.1.54±0.06and APP protein:0.65±0.02vs.1.78±0.03, Aβ protein:0.12±0.00vs.1.32±0.24, BACE-1protein:0.36±0.03vs.1.52±0.02allP<0.05).Conclusions Mild hypothermia after trauma brain injury(TBI) in rats may be promote the degradation of BACE-1and reduce its activity to reduce high expression of Aβ caused secondary brain injury,which play a neuroprotective role.