| Objective: Alzheimer’s disease,also known as Alzheimer’s disease（AD）,is a neurologic disease caused by chronic degenerative injury of brain tissue.With continuous memory reduction and recognitive and behavioral disorders as the main clinical features,hidden onset and long course of disease,which is a universal medical problem.in the word.At present,cholinase inhibitors and amino acid receptor antagonists are mainly clinical patients to deal with AD.However,these drugs have certain limitations,high long-term use cost,poor patient compliance,can only appropriately improve clinical symptoms,and have serious adverse reactions.Because of the neurons during the pathological process of AD The damage is often irreversible,and the course of the disease is also difficult to reverse the learning ability.Therefore,for the prevention and treatment of AD,the early intervention measures are the focus of the research.In recent years,scholars at home and abroad have conducted a lot of studies on the influence of repeated transcranial magnetic stimulation（rTMS）on cognitive function.The results show that rTMS can improve the cortical excitability of patients with mild to moderate AD,promote cortical nerve repair and functional remodeling,effectively improve cognitive [6] in patients,and become a crucial subsidiary means for the clinical prevention and remedies of AD.In this study,the neuroinflammatory response to AD was used to investigate the rats of E-CET on D-galactose-induced AD-like model combined with rTMS The effect of learning and memory ability,aims to elucidate the mechanism of electroacupuncture combined with rTMS on improving learning and memory ability and hippocampal neuroinflammatory response in AD-like rats,and to provide experimental basis and theoretical support for the clinical promotion of electroacupuncture combined with rTMS to prevent AD.Methods: Four-month-old SD rats were selected,male,with body mass of 370-390 g,ventilated feeding environment,appropriate temperature,uniform light,free feeding and drinking water.After 1 week of adaptive rearing,the rats were divided into normal,model,needle,repetitive and needle + TMS with 8 mice per group.AD-like model rat was prepared using D-galactose [120 mg/kg.d] for 8 weeks except the normal group.After the molding,（1）the electric needle group（EA）gave acupuncture "Baihui" point and "Renyu" point at 15° Angle "Baihui" 3-4 mm,"kidney yu" 3-4 mm toward the spine.After acupuncture,connect the HANS-200 A electric needle instrument,a group of wires are respectively connected to "Baihui" point and one "Renyu" point,left and right "Renyu" point alternate day(with.For continuous wave,the frequency needle is 50 HZ,current 1 m A,with acupuncture local fibrillation.（2）Repeat transcranial magnetic group（rTMS）: use the type YRD CCY-1 type electromagnetic stimulator,and choose the focus type "8" word coil.The rat head was fixed to the fixation tube,and the coil was pressed close to the left prefrontal lobe of the rat skull,and was tangent vertically to stimulate the frequency For 5 HZ,maximum output intensity of 90%,repeated pulse magnetic stimulation of 100 strings.（3）Electroacupuncture + transcranial magnetic（EA + rTMS）group: repeated transcranial magnetic stimulation after electroacupuncture treatment,the method and stimulation parameters are the same as the EA group and rTMS group,the above intervention once / day,a total of 2 weeks.Normal and model groups underwent synchronous grasping and fixation during the intervention treatment.After the end of the intervention,the rats were tested behaviorally using the Morris water maze experiment.Completed the behavioral test,appropriate rats were selected for tissue and perfusion samples.Rat postsynaptic observation in the hippocampus Compact band thickness;the number of activated microglia in the rat hippocampus was determined by immunohistochemical staining,and the protein expression levels of Iba-1,TNF-,IL-6 and IL-1 were determined by Western Blot.Result: 1.Repeated rTMS can improve learning and memory in D-galactose-induced AD-like rats Results from Morris water maze experiment’s date : there was no difference between the ratio of the second day and electroacupuncture（P<0.01）;the difference（P<0.01）,indicating that the rats had gradually found the platform through learning and memory during continuous learning training.In the spatial exploration experiment,the model group explored significantly shorter in the target quadrant than the remaining group,and the difference was very significant（P <0.01）;The EA + rTMS group explored significantly longer in the target quadrant than the EA and rTMS groups,with significant differences（P <0.01）.2.Repeated rTMS can improve learning and memory in D-galactose-induced AD-like rats The comparison of the postsynaptic dense zone in each hippocampus showed that the difference was statistically significant（P <0.01）in the model group and significantly（P < 0.01）in the electroneedle and MS（P <0.01）.3.The combination of repeated rTMS can inhibit D-galactose-induced activation of microglia in the hippocampus of AD-like rats Immunohistochemical test results: compared with the normal one,microglia increased in the difference（P <0.01）;compared with the model group,the number of activated microglia was decreased,significantly（P <0.01）,and significantly（P <0.05）.4.Preelectroneedle was able to improve D-galactose-induced neuroinflammatory responses in the hippocampus of AD-like rats WB test results: TNF-,IL-6 and IL-1 in the hippocampus,expression of each intervention（P <0.01）,EA and rTMS in EA and rTMS（P <0.01）.conclusion: 1 Electroacupuncture combined and repeated rTMS can effectively improve the spatial capacity and memory capacity in D-galactose-induced AD-like rats.2.The combination of electroacupuncture and repeated TMS can regulate the thickness of the postsynaptic dense zone in the hippocampus,and the postsynaptic dense zone in AD rats after the combination of both methods,which improved the studying capacity and memory capacity of the rats.It shows that the increase of postsynaptic dense zone by regulating the inflammatory response,and then improves the spatial learning and behavior ability in rats.3.The combination of repeated rTMS can reduce the expression of specific protein Iba-1 in D-AD-like pathological model,indicating that the combination of rTMS can inhibit the activation of microglia in AD-like rats,which may be the mechanism by which the combined rTMS can improve neuroinflammatory response in rats.4.The D-galactose-induced proinflammatory factor-TNF-,IL-6 and IL-1,indicating that repeated rTMS can improve the neuroinflammatory response in AD-like rats,which may be one of the mechanisms to improve the learning and memory capacity of AD-like rats. |
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