| Background:Alzheimer's disease is a common clinical and frequently occurring disease.So far there is no effective treatment of drugs.A? cascade theory is one of the more commonly accepted hypothesis of pathogenesis of AD,the theory that extracellular beta amylase A? excessive deposition is the key to the pathogenesis of AD.And more and more evidence shows that AD and transgenic animals within the brain neuronal autophagic dysfunction,a large number of autophagosomes and autophagosomes gathered in the cells to become A? production,aggregation sites,resulting in axons Functional impairment,synaptic damage,and even autophagic neuronal death.LC3II is a marker of autophagy that interacts with the autophagy selective substrate P62 to form a protein complex that eventually undergoes autophagic degradation in a P62-dependent manner.Therefore,LC3 ? and P62 in the process of autophagy at the end of a synergistic effect,together reflect the level of autophagic activity.Our preliminary experiment confirms the hypothesis that EA reduces the overall level of A? in brain tissue of AD model mice and has the possibility of influencing autophagy-acupuncture can inhibit intracellular autophagic accumulation and protect cells from A? toxicity."Kidney qi deficiency,phlegm obscure" is the main pathogenesis of AD.AD pathological products A?,should be endogenous phlegm.A? oligomers of neurotoxicity,leading to cognitive dysfunction,its mechanism and the Chinese brain"phlegm blinded brain surgery" pathogenesis similar.Kidney qi deficiency,gasification of the micro-performance may be due to neuronal autophagic dysfunction,is the pathogenesis of AD.Acupuncture "Yishen Quxu Tongqiao" treatment of AD micro-basis may be to adjust the disorder of autophagy,reduce the brain Ap levels,so as to effectively prevent and control AD.In this study,the APP/PS1 double transgenic mice were used as the animal model of AD,and the learning and memory behavior and autophagy level of AD mice were observed on the basis of the reduction of the key markers of AD,AD pathogenesis and acupuncture treatment of AD mechanism for the acupuncture "Yishen Qudu" method to provide AD experimental basis.Objective:Taking EA at Baihui(DU20),Yongquan(K1)on six weeks of APP/PS1 Transgenic mice as animal models of AD to investigate the effect of Electroacupunctureure on learning and memory ability and its mechanism related to autophagic receptor p62 in APP/PS1 Transgenic mice.Methods:The 7-month-old APP/PS1 transgenic mice were equally and randomly divided into model group and EA treatment group and negative transgenic mice were selected into the nomal control group.EA was applied to "Baihui"(GV 20)and "Yongquan"(KI 1)for 15min,once every other day for 6 weeks.The learning-memory ability was detected by using Morris water maze testing,hippocampal LC3? and P62 were detected using Western blot(WB).Remove the brains to make and observe the hippocampal CA 1 area transmission electric lens.Results:1.Results of Morris water maze test showed that there was no significant difference in platform quadrant length(P>0.05).Compared with the normal control group,the model group increased(P<0.01).There was no significant difference between acupuncture and model group in escaping latency,but it was found that the incubation period of acupuncture group was shortened,and the whole time curve showed a decreasing trend compared with the model group,which indicated that electroacupuncture had the effect of improving learning and memory ability.With the increase in the number of training days,the control group compared with the other groups were significantly different(P<0.05).2.Western blot results showed that there was significant difference between the LC3? of the three groups(P<0.05)and there was no significant difference between P62 of the three groups(P>0.05).Compared with the control group,the expression of LC311 in the model group increased(P<0.05).Compared with the model group,the expression of LC3 ? was decreased and the expression of P62 was increased(P<0.05),and the expression of P62 was decreased in the acupuncture group(P<0.05),indicating that acupuncture group can inhibit the accumulation of autophagy bubble,reduce autophagic abnormalities,and 7 months of mice autophagy lysosomal fusion and degradation function is still normal.3.Senile deposit was seen in hippocampus of transgenic mice,mainly classic deposits composed of amyloidy core and surrounding dystrophic neurities,and diffuse deposits was also seen.Weak positive staining around some microvessels was observed.There were abundant autophagosome and late lysosome in dystrophic neuritis and neurons,which present the disordered autophage/lysosome method.Conclusion:The double transgenic APP/PS1 mice mimic AD pathologic hallmark such as senile plaques and cerebral amyloid angiopathy.EA intervention can effectively down-regulate LC3 II and P62 expression and improve learning and memory abilities in APP transgenic model mice,which may contribute to its effect in inhibiting neuronal autophagy... |
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