Mechannism Research Of Guben-Jiannao Method In Rat With AD Based On The Effect Of SorLA On APP Hydrolysis Pathway

ObjectiveWith the rapidly aging population,Alzheimer's Disease?AD?is becoming more and more widely attention,because of its high prevalence,mobidity and impact on the society and their families.Therefore,the globe has realized the importance of strengthening related studies of Alzheimer's Disease in order to research and develop effective control measures.our study intends to explore the treatment and mechanism of AD Guben-Jiannao Method,then explain the scientific connotation of Guben-Jiannao Method and provide experimental basis and clinic guidance for this method.MethodsWe brought 90 clean Wistar rats aged of 12 months,We divided them randomly into 7 groups.Such as normal group,blank control group,model group,Guben-Jiannao fluid high does group,middle group,low group and Aricept group,12 in each group.Normal group would be processing.Model group and treatment groups were given injection concentration of 5ug/ul A?_1-42-42 in bilateral hippocampal brain stereotaxic to copy AD model,blank control group rats were given physiological saline injections by the same place and does.After 3 says,each treatment group and model group had been given corresponding drug lavage by respective according to the10ml/kg.d for 4 weeks.Blank control group and model group had been given saline lavage in accordance with the same does for 4 weeks.After four weeks treatment,the learning and memory ability was tested by Morris water maze test in Rats.Enzyme linked immunosorbent assay?ELISA?method was used to detect the levels of A?_1-42in hippocampus.Levels of SorLA and SNX27 in hippocampus were detected by Real-time PCR and Immunofluorescence technique.Levels of APP in hippocampus were detected by Immunofluorescence technique.Results1 In navigation experiment,in incubation period of the model group rats to find hidden underwater platform was longer than blank control group?P<0.01?,the incubation period of treatment groups were shorter than the model group?P<0.05?.Percentage comparison of target quadrant swimming time of model group significantly lower than the blank control group?P<0.01?,the treatment groups were higher than normal group?P<0.05?.In space exploration experiment,the model group rats to find the original sets of the incubation period significantly longer than the blank control group?P<0.01?,the incubation period in treatment group were higher than that of model group?P<0.05?.Model group rats through the original position significantly less than blank control group?P<0.01?,the incubation period in treatment group were more than model group?P<0.01?.To compare with blank control group,Target quadrant swimming time percentage of model group was significantly lower?P<0.01?,that of the treatment group were higher than that of model group?P<0.05?.2 By Enzyme linked immunosorbent assay Method,we found that the expression of A?_1-42-42 was of model group was significantly more than that in blank control group?P<0.01?;After 4 weeks,the expression of A?_1-42-42 was less in Guben-Jiannao high,middle and Aricept group?P<0.05?.3 By Real-time PCR,we found that the expression of SorLA and SNX27 m RNA was in model group was lower than that in blank control group?P<0.01?;After 4weeks,we found that the expression of SorLA and SNX27 was more than that in model group?P<0.05?.4 By Immunofluorescence technique,the expression of SorLA and SNX27 in model group was less than that in blank control group;After 4 weeks,the expression of SorLA and SNX27in treatment groups were more than that in model group except Guben-Jiannao low group.Conclusion1 After the modeling,the model group rats'learning and memory ability decreased significantly,the expression of A?_1-42-42 increased significantly.It shows that the AD model in aged rats have been manufactured successfully.2 Guben-Jiannao Method can improve the learning and memory ability,reduce the expression of A?_1-42,increase the expression of SorLA and SNX27 mRNA and the number of SorLA and SNX27 combinations in hippocampus of rat.3 Guben-Jiannao Method has a definite curative effect on AD.Because It can increase the expression of SorLA and SNX27,increase the number of SorLA and SNX27 combinations,then reduce the expression of A?,inhibition and elimination of A?production and deposition.To avoid the play of its neurotoxicity and then appear AD characteristic pathological changes.