| Objective:1.Evaluate the improvement of learning and memory ability of chronic ketamine treated rats after electroacupuncture.2.Observe and compare the changes of neuron structure of hippocampus and parietal cortex after the treatment of chronic ketamine.3.Observe and compare the expression of APP,BACE1 and PSEN1 in the neurons of hippocampus and parietal cortex after the treatment of chronic ketamine.Then,the possible mechanism of electroacupuncture on the improvement of learning and memory function and the regulation of related proteins in rats,with chronic ketamine administration,is explored to provide relevant basis for the treatment of side effects of chronic ketamine administration.Methods:SPF SD male rats are randomly divided into 4 groups with 8 rats in each group,including normal group?N?,saline group?S?,ketamine group?K?,and ketamine+electroacupuncture group?KE?.The group N is not treated.The group K and group KE are intraperitoneally injected once a day at 9 am for 7 days,with ketamine hydrochloride at a dose of 50mg·kg-1.The group S is intraperitoneally injected once a day at 9 am for 7 days,with saline at a dose of 2.5ml·kg-1.In the group KE with a14-day course of treatment,the acupoints are taken for electroacupuncture treatment 30minutes after ketamine administration every day.After the drug is stopped,the acupuncture is continued for 7 days.No treatment is given to the remaining three groups.A 0.25mm×25mm filiform needle,with frequency 2Hz and current 1mA,is used to pry sanyinjiao point and zusanli point once a day for 30min,while alternating left and right electroacupuncture.At the end of electroacupuncture treatment,rats in each group are tested with water maze for 6 days.At the end of treatment,the spatial learning and memory ability of rats are observed and compared.Nissl staining is used to observe the changes of neuron structure in hippocampus and parietal cortex.The expression of APP,BACE1 and PSEN1 are detected by immunohistochemistry and Western blotting respectively in the hemilateral brain of each group of rats.The difference of the expression between groups are compared and analyzed.Results:1.Water maze test results:in the first five days of water maze navigation test,the escape latency of group K and group KE is significantly longer than group N?P<0.05?.The escape latency of group KE is shorter than group K?P<0.05?.Compared with the group N,the time of staying in the virtual platform quadrant and the times of crossing the virtual platform in the group K decreased significantly?P<0.05?.The time of staying in the virtual platform quadrant and the times of crossing the virtual platform in group KE increased slightly?P<0.05?.2.Nissl staining results:the neurons in hippocampus and parietal cortex of group N and group S are arranged in order.The structure is relatively complete.The membrane edge of neurons in hippocampus and parietal cortex of ketamine group are fuzzy.The nucleus,synaptic morphology and Nissl body are not easy to recognize.Some cells are vacuolated.The structure of neurons in hippocampus and parietal cortex of group KE is close to group N.3.Results of immunohistochemistry:compared with group N,there is no significant difference in the number of APP,BACE1 and PSEN1 positive cells in the hippocampus and parietal cortex of group S.The number of APP,BACE1 and PSEN1 positive cells increased significantly,in hippocampus and parietal cortex of group K and group KE?P<0.01?.Compared with the group K,the number of APP,BACE1,PSEN1 positive cells,in the hippocampus and parietal cortex of the group KE decreased significantly?P<0.01?.4.Western blotting results:compared with the group N,there is no significant difference in the expression of APP,BACE1 and PSEN1 in the hippocampus of the group S.The expression of APP,BACE1 and PSEN1 in the hippocampus and parietal cortex of the group K,and the group KE increased significantly?P<0.01?.Compared with the group K,the expression of APP,BACE1 and PSEN1 in the hippocampus and parietal cortex of the group KE increased significantly?P<0.01?.Conclusion:The learning and memory ability of chronic ketamine treated rats can be improved,and the abnormal changes of neuron structure in hippocampus and parietal cortex can be changed by Electroacupuncture.Meanwhile,the overexpression of APP,BACE1 and PSEN1 proteins in hippocampus and parietal cortex,induced by ketamine,is down-regulated,that may be the potential mechanism of electroacupuncture in improving spatial learning and memory ability and abnormal changes in neuron structure in rats. |
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