| Objective:Under the guidance of the theory of acupuncture and moxibustion,this experiment explored the effect of electroacupuncture at Baihui and Shenshu points on the learning,memory and cognitive impairment of Alzheimer's disease like rats induced by D-galactose,and further studied whether its mechanism of action could induce autophagy by regulating the PI3K / Akt / mTOR axis of autophagy related pathway,promote the removal of neurofibrillary tangles in hippocampal neurons,and alleviate neurites Touch injury can improve the learning and cognitive ability of Alzheimer's disease like rats,and provide scientific experimental basis for promoting and popularizing acupuncture to prevent ad.Methods:A total of 48 male SD rats were randomly divided into a blank control(BC)group,a model group,a electro-acupuncture(EA)group and a sham electro-acupuncture(SE)group,with 12 rats in each group.Except for the BC group,the other groups were given D-galactose intraperitoneal injection for 7 weeks to establish AD-like model.After daily intraperitoneal injection,the EA group and the SE group were needled GV20 and BL23 for 20 minutes,and connected the electro-acupuncture therapeutic apparatus.The EA group was electrified after needling,while the SE group penetrated the skin only and did not electrify.After intervention,Morris water maze and open field test were used to evaluate the learning and cognitive ability of each group.The synaptic numerical density in hippocampus was detected by transmission electron microscopy,the expression of PHF-1 in hippocampus was detected by immunohistochemistry,and the expression of PI3K,AKT,P-AKT and mTOR were detected by Western blotting.Results:1.In the navigation experiment,on the first day,there was no significant difference in escape latency(P > 0.05),but with the increase of training days,the escape latency decreased.Compared with the same time on the 2nd-5th day in the blank control group,the escape latency of rats in the model group and the sham electroacupuncture group was significantly longer(P < 0.01);there was no significant difference in the escape latency on the 2nd day(P > 0.05),the 3rd day(P < 0.05)and the 4TH-5TH day(P < 0.01)in the electroacupuncture group.Compared with the model group at the same time from the 2nd to 5th day,the escape latency of EA group was significantly shorter(P < 0.01),but there was no significant difference between the false EA group and the model group(P > 0.05).Compared with the sham electroacupuncture group,the escape latency of the electroacupuncture group was significantly shorter at the same time(P < 0.01).In the space exploration experiment,compared with the blank control group,the model group and the false electroacupuncture group passed through the original platform quadrant for a long time,the difference was statistically significant(P < 0.01);the electroacupuncture group and its comparative difference was statistically significant(P < 0.05).Compared with the model group,the time ratio of electroacupuncture group after the original platform quadrant increased significantly(P < 0.01);there was no significant difference between the false electroacupuncture group and the model group(P > 0.05).Compared with the sham electroacupuncture group,the time of electroacupuncture group passing through the original platform quadrant was significantly longer(P < 0.01).In the open field experiment,compared with the blank control group,the movement distance,the number of standing up and the movement time in the central area of the rats in the model group and the sham electroacupuncture group increased significantly(P < 0.01),the difference was statistically significant(P < 0.01);the difference between the electroacupuncture group and the sham electroacupuncture group was statistically significant(P < 0.05).Compared with the model group,the movement distance,the number of standing up and the ratio of movement time in the central area of rats in the electroacupuncture group increased significantly(P< 0.01);there was no significant difference between the sham electroacupuncture group and the model group(P > 0.05).Compared with the sham electroacupuncture group,the above indexes in the electroacupuncture group were statistically significant(P <0.01).2.Compared with the blank control group,the number density of synapses in the hippocampus of the model group and the sham electroacupuncture group was significantly less(P < 0.01);there was no significant difference between the electroacupuncture group and the blank control group(P > 0.05).Compared with the model group,the density of synapses in the hippocampus of EA group was significantly higher(P < 0.01),and there was no significant difference between the sham EA group and the model group(P > 0.05).Compared with the sham EA group,the density of synapses in EA group was significantly higher(P < 0.01).In the model group,the synaptic structure of neurons in the hippocampus was fused,the density of the posterior membrane was sparse,the boundary of the anterior and posterior membrane was unclear,and the number of complete synapses was reduced;the pathomorphology of the hippocampus in the electroacupuncture group was better than that in the model group,and the synaptic structure of neurons in the hippocampus in the electroacupuncture group was restored to near normal level.3.Compared with the blank control group,the expression level of PHF-1 in the hippocampus of the model group and the sham electroacupuncture group was significantly higher(P < 0.01);there was no significant difference between the electroacupuncture group and the blank control group(P > 0.05).Compared with the model group,the expression level of PHF-1 in the hippocampus of rats in the electroacupuncture group was significantly lower(P < 0.01);there was no significant difference between the sham electroacupuncture group and the model group(P > 0.05).Compared with the sham electroacupuncture group,the positive expression of PHF-1 in the electroacupuncture group decreased(P < 0.01).4.Compared with the blank control group,the expression levels of PI3K,Akt,p-Akt and mTOR in the hippocampus of the model group and the sham electroacupuncture group were significantly increased(P< 0.01);there was no statistical significance between the above protein expression and its comparison in the electroacupuncture group(P > 0.05),and there was statistical significance between the sham electroacupuncture group and its comparison(P < 0.05).Compared with the model group,the expression levels of PI3K,Akt,p-Akt and mTOR in the hippocampus of the rats in the electroacupuncture group were significantly lower(P < 0.01);the expression of PI3K in the sham electroacupuncture group was statistically different from that in the model group(P < 0.05),and there was no significant difference in other indexes(P > 0.05).The expression of autophagy related protein in EA group was lower than that in sham EA group(P<0.01).Conclusion:1.Pre acupuncture can improve the spatial learning and memory ability and cognitive function of ad like lesion model rats.2.Pre acupuncture can improve the degree of synaptic damage,increase the density of synapses and promote the regeneration of synapses in the hippocampus of AD-like pathological model rats,which indicates that pre acupuncture may improve the learning and cognitive ability of ad pathological model rats by optimizing the morphological structure of synapses in the hippocampus.3.Pre acupuncture can reduce the synaptic toxicity and improve the learning and cognitive function of rats by inhibiting the pathological deposition of NFTs in the hippocampus of AD-like lesion model rats.4.Pre acupuncture can down regulate the expression of PI3K,Akt,p-Akt,mTOR and induce autophagy.The mechanism may be to regulate PI3K / Akt / mTOR signal pathway,induce autophagy,promote NFTs clearance,reduce synaptic damage,and improve the cognitive function of learning and memory,so as to achieve the role of prevention and treatment of AD. |
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