Effects Of Bradykinin On β-amyloid Protein Induced Alzheimer's Disease Animal Model

Alzheimer's disease (AD) is the most common form of senile dementia. To date no one single model combines all the relevant pathophysiological and behavioural aspects of AD. Investigations were restricted for no suitable animal models. In this study, β-myloid protein(Ap) rats are used as an animal model for AD. And we injected Aβ combination with bradykinin ( BK) , observation BK caused dysfunction of learning and memory and neuronal loss in normal mouse and AD model, respectively.MethodsA total of 25 healthy adult Wister rats, 13 females and 12 males, aged 5 months, weighting 280g 10g. Animals were trained to directly found the platform after they were put into the Water maze. Then rats were randomly divided into 5 groups; (1) normal control group(n =5) (2)distilled water(DW) controlgroup (n =5) (3)bradykinin injection group (n =5) (4)β-myloid protein (Aβ) injection group( n = 5 ) (5)Co - injection of Ap with BK group ( n = 5 ). Lateral hippocampus injection into the dentate gyrus was performed under Chloral Hydrate (300mg/kg) anaesthesia by means of a stereotaxic apparatus ( coordinates; AP = 3. 3; S = 1. 5 from bregma; H = 3. 3 from the dura). Long - term memory was examined 14 days after administration. Animals were perfused by 4% polyformaldehyde. Brain were removed and post fixed in 4% polyformalde-hyde and alcohol, embedded with paraffin, cut into consecutive 7m. The sections were stained with haematoxylin - eosin ( HE) , Nissl stained and the tau deposition was detected using its specific polyclonal antibody. We measured the integrated OD total by using MetaMorph microscope picture analysis system, and used SPSS 11.5 software to process data.Result1. Characteristics of impairment of the performation in the water maze task: There was no significant difference between group. 1. and group. 2. But compared with control goups, latent period was significantly prolonged in group 3.4. (P <0.05). And latent period of group 5 was prolonged compared with others (P<0.05).2. HE and Nissl staining: HE - stained and Nissl - stained section of the hippocampal region produced only slight degeneration surrounding the injection site in A reated group. There is no neuronal change in normal control, distilled water( DW) control and bradykinin injection group. But co - injection of A with BK caused extensive neuronal loss not only around the injection site but also in distant areas. In group 5, HE - stained showed microglia reaction around neuronal loss areas.3. Tau immunohistochemistry stainingThe Tau positive immunoreactivity products in the neurons were scattered in cytoplasm and axis - cylinder. The integrated OD total of Tau positive cell was significantly higher in co - injection of A with BK group than others ( P < 0. 05 ) , not only in CA1 and CA4 of hippocampal but also in cotex. .Conclusion1. Confirmed A-treated rats can produce memory impairment and neuronal dysfunction. But memory impairment is light, neuronal dysfunction effects only exists around the injection site.2. BK - treated rats can also produce memory impairment. But no morpho-logical changes were observed in brain.3. BK injection into Atreated rats hippocampus produce obviously memory lesion and drastic neuronal loss .4. Co - injection of A with BK can produce synergistic action. We may use this method to creat a useful AD model.