Research On The Action Mechanism Of P38MAPK Signal Pathway In Treating The Rats With Alzheimer Disease By Preventative Moxibustion

ObjectiveAlzheimer disease(AD) is a kind of degenerative disease in central nervous system with clinical manifestation of progressive cognition functional disturbance, the decrease of learning and memory ability, affective disorder, behavioral disorder, and the final living self-care disability. AD has become the fourth cause of death besides heart disease, tumor and apoplexy in the aged people. AD morbidity is a serious public health problem because of its rapid increase tendency with nation population aging. The investigative emphasis of AD should turn to early diagnosis and early intervention because of its long course of disease, serious pathogenetic condition, bad therapeutic effect and much cost in the intermediate stage and advanced stage. This study is designed to research on the action mechanism of the inflammatory reaction mediated by p38MAPK signal pathway in treating AD rats by preventative moxibustion. The AD model was established by stereotaxis injecting agglutinated A β25-35into rat’s bilateral hippocampus. The rat with AD was treated by preventative moxibustion at the points of "Baihui"、"Shenshu" and "Zusanli". MethodsFifty normal male SD rats with15months old, weighing350-480g were selected. Firstly they were detected with the method of Y type water maze to reject the rats with too clumsy or too sensitive reaction. The qualified rats were randomly divided into normal group, sham-operation group, model group and pre-moxibustion group, with10cases in each group. After the preventative moxibustion treatment at the points of "Baihui"、"Shenshu" and "Zusanli"(left and right "Shenshu","Zusanli" respectively alternative use every other day)for3therapy courses (moxibustion for5minutes at each point, once daily with6days a course and one day rest between two courses), the rats in pre-moxibustion group were established into AD models by stereotaxis injecting agglutinated Aβ25-35in the bilateral hippocampus. Then continue the preventative moxibustion treatment for one course after the model production. The learning and memory ability was tested in the ethology experiment by Morris water maze, the nerve cell ultrastructural change of hippocampus CA1zone in rats were observed by transmission electron microscope, the expression change of P-p38MAPK、COX-2、PGE2of hippocampus zone in rats were observed by immunohistochemical method of SP. All data were put into the computer and analyzed by SPSS13.0statistical package. The experiment results were expressed as mean±standard deviation (x±s).Results(1) From the experiment of Morris water maze, we discovered that the escape latent period shortened gradually in each group as the swimming days increased, which indicated that the rats in each group had a certain learning and memory ability to search the platform in the5days’swimming training, but the ability had major disparities. After stereotaxis injecting agglutinated A β25-35into rat’s bilateral hippocampus, the average latent period of five days and the last three days remarkably lengthened, and the times of going through the original platform decreased obviously in model group. In the location sea trial and space search test, the quadrant percentage remarkably lowered in the rats of model group. There were significant differences compared with normal group and sham-operation group (P<0.01). The results showed that the rats’ ability of learning and memory seriously damaged in model group and the model was successful. After the preventative moxibustion treatment, the average latent period of five days and the last three days remarkably shortened, the times of going through the original platform increased obviously, and the quadrant percentage remarkably heightened in the rats of pre-moxibustion group. There were significant differences compared with model group (P<0.01). The results indicated that preventative moxibustion was a kind of effective method in preventing the learning and memory dysfunction. Preventative moxibustion had obvious function in ameliorating the learning and memory ability of the rats with Alzheimer disease.(2) Transmission electron microscope showed that in the hippocampus CA1zone of the rats in normal group and sham-operation group, cell membranes of nerve cells were integrated, electron density of cytoplasm and organelles were well-distributed, mitochondrion structures and mitochondrial crista were clear, endoplasmic reticulum of inter organelle lined up in order. In the hippocampus CA1zone of the rats in model group, we observed some nerve cells degenerated by transmission electron microscope, cell membrane shrinked, the volume of the cell contracted, electron density in cytoplasm and organelle densed, nuclear membrane space widened, endoplasmic reticulum of inter organelle expanded and mitochondrion swelled, even mitochondrial crista deformed or deleted. However, in the hippocampus CA1zone of the rats in pre-moxibustion group, cell nucleus was almost normal and mitochondrion in organelle swelled a little. Mitochondrion, dictyosome and ribosome remarkably increased compared with model group. Preventative moxibustion had obvious function in ameliorating the cataplasis of neuron ultrastructure.(3) The positive cells expression of P-p38MAPK、COX-2、PGE2in hippocampus zone of rats in model group obviously increased, showing the gradation value of the positive cells obviously lowered. There were significant differences compared with normal group and sham-operation group (P<0.01).The positive cells expression of P-p38MAPK、COX-2、PGE2in hippocampus zone of rats in pre-moxibustion group obviously decreased, showing the gradation value of the positive cells obviously heightened. There were significant differences compared with model group (P<0.01).ConclusionInjecting agglutinated A β25-35into the bilateral hippocampus can activate the p38MAPK signal transduction pathway. The activation of p38MAPK results in the up-regulation of inflammation mediators COX-2、PGE2to induce the retrogression change of the brain neurons in the rats with AD and finally cause the learning and memory dysfunction. Preventative moxibustion can decrease the positive cells expression of P-p38MAPK、COX-2、PGE2in hippocampus zone, restrain the nerve cell damage and degeneration caused by injection of Aβ, promote the recovery of nerve cells and obviously ameliorate the cataplasis of neuron ultrastructure. Restraining the p38MAPK signal pathway, relieving the expression of inflammation mediators COX-2、PGE2so as to protect and recover the brain neurons and finally improve the learning and memory ability, which may be the action mechanism of prevention and cure AD by preventative moxibustion.