| ObjectiveTaking the APP/PS1 transgenic mouse model as study subjects,two acupoints,"Baihui"and "Shenyu," are used as the intervention method.This study observes the behavioral changes,histopathological changes of the frontal lobe,and expression of inflammatory factors(TNF-αand NF-κB)in the model group,electroacupuncture group,western medicine group,and electroacupuncture+ western medicine group.The goal is to investigate the partial mechanism of electroacupuncture in improving cognitive dysfunction and neuroinflammatory response in APP/PS1 mice.MethodsForty APP/PS1 double transgenic male mice,aged six months,are selected along with ten C57BL/6J male mice of the same age.The forty APP/PS1 transgenic mice are divided into four groups according to a random number table method:the electroacupuncture group,model group,western medicine group,and electroacupuncture+western medicine group,each containing ten mice.Ten C57B L/6J mice are used as the control group.Following the principles of Experimental Acupuncture,electroacupuncture stimulation is administered at the Baihui point(midpoint of the line connecting the two ears)and the Shenyu point(about 7 mm from the second lumbar vertebra).Western medicine was selected as donepezil hydrochloride.(ⅰ)The blank group and the model group were given 1 mg/kg distilled water gavage;(ⅱ)the electroacupuncture group was given 0.5-inch acupuncture needles(0.30×0.25 mm),3 to 5 mm flat stabbing at Baihui and straight stabbing at bilateral Shenyu,connected to an electroacupuncture instrument,sparse and dense wave,frequency 2 Hz,current 1-2 mA,stimulated for 15 min;(ⅲ)the western medicine group was given donepezil 1 mg/kg gavage;(ⅳ)electroacupuncture+western medicine group:electroacupuncture was given to stimulate Baihui and Shenyu for 15 min,and donepezil 1 mg/kg was given by gastric gavage.All the interventions were performed once a day for 28 d.Before and after the interventions,Morris water maze experiments were performed on each group of mice.After the intervention,frontal lobe tissues were taken,HE staining was performed to observe the pathological changes of the frontal lobe,and Western Blot was performed to observe the expression of inflammatory factors.(TNF-α and NF-κB)Result1.Results of the Morris water maze experimentFrom the analysis of pre-intervention data:compared with the blank group,mice in the model group,electroacupuncture group,western medicine group,and electroacupuncture+western medicine group had longer evasion latency(P<0.05),shorter residence time in the target quadrant(P<0.05),and fewer times of crossing the platform(P<0.05).From the analysis of the data after the intervention:compared with the blank group,the mice in the model group had a longer escape latency(P<0.05),fewer times of crossing the platform(P<0.05),and a shorter stopping time in the target quadrant(P<0.05);compared with the model group,the electroacupuncture group,the western medicine group,and the electroacupuncture+western medicine group all showed a shorter escape latency(P<0.05),an increase in the stopping time in the target quadrant(P<0.05),and an increase in the number of crossing the platform(P<0.05).Comparisons were made between the electroacupuncture group,the western medicine group,and the electroacupuncture+western medicine group,and there was no statistical difference between the three groups(P>0.05).A comparison of the mean values of the three groups revealed that the behavioral performance of mice in the electroacupuncture+western medicine group was more robust than that in the electroacupuncture and western medicine groups.From the analysis of mice swimming trajectory map:in the positioning navigation test,compared with before intervention,the swimming trajectory of the electroacupuncture group,western medicine group,and electroacupuncture+western medicine group was shorter,the total distance was shortened and purposeful;in the spatial exploration experiment it was seen that the swimming trajectory of mice in the three groups was primarily concentrated in the target quadrant and purposeful to find the platform,and there was no significant change in the swimming trajectory of mice in the model group before and after the intervention.2.HE resultsThe neurons in the blank group were evenly distributed,with full cell morphology and clear layers.Compared with the blank group,the neurons in the model group were arranged in a disorganized and loose manner,with a reduced number of cell layers and fewer pyramidal cells;Compared with the model group,the nerve cells in the western medicine group,the electroacupuncture group and the electro-acupuncture+western medicine group were more neatly arranged,with less atrophy and edema.Compared with the model group,the neuronal cells in the western medicine group,the electroacupuncture group,and the electroacupuncture +western medicine group were arranged more neatly,and the atrophy and edema were reduced.Compared with the electroacupuncture group and the western medicine group,the mouse cortical cells in the electroacupuncture+western medicine group were smoother and more regular in outline,more neatly arranged and compact,with fuller cytosol and richer cytoplasm.3.Western BlotThe expression of TNF-α in the frontal lobe tissue of mice:the content of TNF-α in the model group was more than that in the blank group(P<0.05);compared with the model group,the expression of TNF-α in the Western medicine group,the electroacupuncture group and the electroacupuncture+Western medicine group were all decreased(P<0.05).When compared among the three treatment groups,the expression of TNF-α in the frontal lobe of mice in the electroacupuncture group was slightly more than that in the Western medicine group(P<0.05).The expression of TNF-α in the frontal lobe of mice in the electroacupuncture group was slightly more than that in the Western medicine group(P<0.05);compared with the Western medicine group,the expression of TNF-α in the frontal lobe of mice in the electroacupuncture+Western medicine group was significantly decreased(P<0.05).The expression of NF-κB in the frontal lobe of mice:the content of NF-κB in the model group was more than that in the blank group(P<0.05);compared with the model group,the expression of NF-κB in the Western medicine group the electroacupuncture group and the electroacupuncture+ Western medicine group were all decreased(P<0.05).When compared among the three treatment groups,the expression of NF-κB in the frontal lobe of mice in the electroacupuncture group was slightly more than that in the Western medicine group(P<0.05);compared with the Western medicine group,the expression of NF-κB in the frontal lobe of mice in the electroacupuncture group was slightly more than that in the Western medicine group(P<0.05).The expression of NF-κB in the frontal lobe of mice in the electroacupuncture+western medicine group was significantly decreased compared with that in the western medicine group(P<0.05).Conclusion1.The comparison of the water maze experiment results for the model group and the electroacupuncture group before and after the intervention demonstrates that electroacupuncture stimulation of "Baihui and Shenyu" can improve the cognitive dysfunction of APP/PS1 mice.2.Electroacupuncture stimulation of "Baihui and Shenyu" can improve neuroinflammation to a certain extent,reduce the expression of TNF-α and NF-κB inflammatory factors,and achieve neuroprotection,which leads to improved cognitive function and learning,and memory ability.This outcome may be related to the amelioration of chronic inflammation in the nervous system through the electroacupuncture stimulation of "Baihui and Shenyu."3.Compared with the model group,the edema and necrosis of frontal neurons were reduced in the electroacupuncture group and electroacupuncture+western medicine group,indicating that the mechanism of action of electroacupuncture to improve the cognitive function of APP/PS1 mice may be related to its protective effect on frontal neurons.4.Compared with the western medicine group,the electroacupuncture group+western medicine group had more advantages in improving cognitive function. |
