| Objective: Alzheimer's disease is a neurodegenerative disease,which closely related with age.Its major clinical manifestations is memory impairment,cognitive impairment and language dysfunction,even as personality and behavior disorders,which made the patient's life quality drop rapidly,and causes the great trouble to its oneself and the family. Therefore, it is necessary to find an effective treatment of AD immediately.The study of brain PET imaging in patients with AD shows that,the glucose metabolism rate of frontal lobe and temporal lobe in AD patients was significantly decreased,while,after the treatment of acupuncture, the rate of glucose metabolism increased.So, we believe that acupuncture is an effective method for the treatment of senile dementia. And its mechanism may be related to changes in brain blood flow and glucose metabolism.At present, the study on the mechanism of AD mainly include amyloid protein ? deposition and Tau protein theory, and some scholars have put forward the hypothesis of mitochondrial cascade,who thinks AD is closely related with mitochondrial damage.Now,the research on mitochondrial is mainly about the function and morphological structure.For the mitochondrial function,the predecessors already had a lot of research,while the research of mitochondrial morphological is very popular. For example,the recent research reports that,the abnormity of mitochondrial's fission and fusion can lead to Parkinson's disease,Alzheimer's disease,Huntington's disease and other neurodegenerative diseases.In the high energy demands region, the dynamic process of mitochondrial fusion and fission and are closely related with synaptic and dendritic spines.When the mitochondrial fission dominates,it can increase the formation of synapses;when the mitochondrial fusion is dominant, it causes the number of mitochondria and synapses reduced.When the mitochondrial fusion and division is abnormal,it will block the transport of mitochondria in neurons,decreased mitochondrial energy metabolism,so as to increase the reactive oxygen species.These changes may, in turn, act on the cellular pathway,disrupted the cell signaling pathway,which leads to the decrease of the function of the synapse and even cause the death of neurons.So our study selected three indexes from the point view of mitochondrial dynamics, the mitochondrial fission protein Drp1, the fusion protein OPA1 and the matrix protein Cypd,to observe the effect of acupuncture at Si-Guan points on these protein in the frontal lobe of AD model rats,to explore the possible pathogenesis of AD and the therapeutic effect and possible mechanism of acupuncture at Hegu and Taichong points in the treatment of AD.Methods: Selected 60 male SD rats aged two months,divide them randomly into blank group, sham operation group, model group, acupuncture group and aricept group,12 rats in each group.AD model was constructed by the method of intracerebroventricular administration of streptozotocin( STZ) in model group,acupuncture group and aricept group.While,the rats of sham operation group were injected citric acid/sodium citrate buffer.The rats in blank group,sham operation group and model group were treated with routine feeding without any treatment;The rats of the acupuncture group,are acupunctured at LR-3 and LI-4 on both sides,stabbed 2-3 mm, each acupoint retained for 15 min.The treatment lasts four weeks,6 days for treatment,1 day for rest.The aricept group were given a gavage of donepezil Hydrochloride Tablets of 0.45mg/kg as the same course of acupuncture treatment.After the intervention, the Morris water maze test was carried out in rats,and compare the behavior of rats with different intervention measures.Quantitative RT-q PCR method was used to detect the expression level of Drp1,OPA1 and Cyp D in rat frontal lobe.And detected the protein expression of Drp1,OPA1 and Cyp D in brain frontal lobe tissue by Blot Western.Observe the effect of acupuncture at Si-Guan points on the expression of these proteins.Results:1.Morris water maze test results:1.1. Place navigation test:The escape latency of rats of groups are shorter with the increase of training days in place navigation test.Compared with the blank group and shame operation group, the escape latency of the model group's rats were significantly prolonged(P<0.01);There are no significant difference between blank group and shame operation group(P>0.05).The escape latency of rats of the aricept and acupuncture group were shorter than model group(P<0.01);But there are no significant difference between aricept group and acupuncture group(P>0.05).1.2 Spatial probe test:According to the results of space exploration test, the number of model rats through the original machine area is less than the blank and shame operation rats(P < 0.01), while,the number of crossing platform in the acupuncture group's and aricept group's rats were more than the model group's(P < 0.01).there are no significant difference between aricept group and acupuncture group(P>0.05).2.Western Blot test:2.1 Compared with other four groups,the protein expression of Drp1 and Cypd showed an increasing trend in the model group,but there was no statistical difference between the model group and the other groups.After acupuncture and drug treatment,the expression of these proteins was down regulated.2.2 The result of OPA1 is opposite with Drp1 and Cypd protein.3.RT-qPCR detection:3.1 The expression of Drp1 and Cypd gene in model group were increased compared with the other four groups,and he difference was statistically significant(P<0.001).But the expression of Drp1 in the aricept group and acupuncture group was higher than that in the sham operation group(P<0.001),while,the expression of Cypd in the two groups was less than that in the sham operation group.And the reduction in the acupuncture group was more than that in the aricept group(P<0.001).3.2 The result of OPA1 is opposite with Drp1 and Cypd gene.Conclusions: Acupuncture at Si-Guan points can significantly shorten the escape latency of AD rats,increase the number of cross platform of AD rats in the space exploration experiment,which suggested that acupuncture at Si-Guan points can improve learning and memory ability of AD model rats.At the same time,acupuncture at Si-Guan points can significantly down regulate the expression of Drp1 and Cypd and increase the expression of OPA1.It is suggested that acupuncture at four points can regulate the imbalance of mitochondrion division and fusion in the frontal lobe. |
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