| Objective:This study investigated the effects of electroacupuncture "" Baihui "" and "" Zusanli "" on the learning and memory abilities of SAMP8 mice,as well as the regulatory mechanisms on the AGER / LRP1 receptor system in SAMP8 mice,to provide an experimental basis for clinical application of electroacupuncture to treat mild cognitive impairment.Methods:Seven month old male SAMP8 mice were used as the research object,and SAMR1 mice of the same genetic background at the same month of age were used as the blank control group.After 1 week of adaptive feeding,all mice were trained in Morris water maze,30 SAMP8 mice with cognitive impairment symptoms were screened,and they were randomly divided into model group(Mod),EA 2Hz group and EA 10 Hz group,10 mice in each group.10 SAMR1 mice served as a blank control group(Con).Referring to experimental acupuncture and a review of the literature,the locations and acupuncture methods of "" Baihui "" and "" Zusanli "" were determined by using an acupoint neurostimulator connected to Baihui and Zusanli respectively,and sparse-dense waves were selected,with the current of 1 m A and the frequency of 2 Hz/10 Hz,each lasting 30 min and once a day for 14 days.The model and blank groups were applied daily with the same degree of grasping and catching restraint at the same time,and no other interventions were provided.At the end of the electroacupuncture intervention,the Morris water maze test(the location navigation test and the space exploration test)was performed for 6 consecutive days.After the water maze was completed,dopamine and norepinephrine content in the cerebrospinal fluid of the mice were measured by microdialysis technique combined with high-performance liquid chromatography.Basic pathological changes of brain tissues and nissl bodies in neuronsin in the hippocampal CA1 region of mice with were observed by neuropathological staining(HE staining and toluidine blue staining).Aβ levels in the cerebrospinal fluid and serum of mice were detected by ELISA,and the protein expression levels of AGER,LRP1,Apo E,NF-κB p65,VCAM-1 and ICAM-1 in the hippocampus of mice were detected by Western blot.Results:Morris water maze:(1)location navigation test: Compared with the blank group,the escape latency of mice in the model group was significantly longer(P<0.01),and compared with the model group,the escape latency of mice in the EA 2Hz group was shorter(P<0.05),and EA 10 Hz group was significantly shorter(P<0.01).(2)Spatial exploration experiments: Compared with the blank group,the model group crossed the platform significantly less often(P<0.01)and spent significantly less time in the target quadrant(P<0.01),and compared with the model group,the EA 2Hz and EA 10 Hz groups crossed the platform significantly more often(P<0.01),and the target quadrant spent significantly more time(P<0.01).Microdialysis: Compared with the blank group,the content of dopamine and norepinephrine in the cerebrospinal fluid of the model group was significantly reduced(P < 0.01);compared with the model group,the content of dopamine and norepinephrine in the cerebrospinal fluid of the EA 2Hz and EA 10 Hz groups was significantly increased(P<0.01);compared with the EA2 Hz group,the norepinephrine level in the EA 10 Hz group was significantly increased(P<0.01).Neuropathological staining: Compared with the blank group,the neurons number,pyramidal cell morphology,volume and arrangement in the hippocampal CA1 region of the model mice showed obvious lesions,accompanied by obvious nuclear condensation and the proliferation of glial cells,the number of nissl bodies was significantly reduced or degranulation,and even the disorganization disappeared;after electroacupuncture intervention,the above-mentioned pathological neurons changes in the hippocampal CA1 region of the mice in the EA 10 Hz and EA 2Hz groups were all improved to various degrees,and the improvement was obvious in the EA 10 Hz group.ELISA:Compared with the blank group,the Aβ content in the cerebrospinal fluid and serum of the mice in the model group was significantly increased(P<0.01).In the model group,the content of Aβ in the cerebrospinal fluid of mice was higher than that in the serum(P<0.05);compared with the model group,the Aβ content in the cerebrospinal fluid of the mice in the EA 2Hz group was significantly decreased(P<0.01),the Aβ content in the serum was decreased(P<0.05),and the Aβcontent in the cerebrospinal fluid and serum of the mice in the EA 10 Hz group was significantly decreased(P<0.01).In the EA 2Hz group,the levels of Aβ in cerebrospinal fluid and serum were not statistically significant(P>0.05),and in the EA 10 Hz group,the levels of Aβ in cerebrospinal fluid of mice were lower than those in serum(P<0.05).Western blot: Compared with the blank group,the expression levels of AGER,VCAM-1 and ICAM-1 in the hippocampal tissues of the model mice were significantly increased(P<0.01),the expression levels of LRP1 and Apo E were significantly decreased(P<0.01),and the expression level change of NF-κB p65 was not statistically different(P>0.05).Compared with the model group,the expression levels of AGER,VCAM-1 and ICAM-1 in the hippocampus of mice in each intervention group were significantly decreased(P<0.01),the expression of LRP1 and Apo E were increased(P<0.01 and P<0.05),and the expression level change of NF-κB p65 was not statistically different(P>0.05).Compared with the EA 2Hz group,the expression levels of AGER,VCAM-1 and ICAM-1 in the hippocampus of mice in EA 10 Hz group were significantly decreased(P<0.01),the expression of LRP1 and Apo E were increased(P<0.01 and P<0.05).Conclusions:1.Electroacupuncture at "Baihui" and "Zusanli" can effectively improve the learning and memory abilities of SAMP8 mice,increase their cerebrospinal fluid DA and NE levels,and reduce their neuropathological damage in the hippocampal CA1 region.2.The mechanism of electroacupuncture "Baihui" and "Zusanli" intervention on mild cognitive impairment in SAMP8 mice may be through improving its AGER/ LRP1 receptor system,which in turn promotes the integrity of the blood-brain barrier and ultimately the clearance of Aβ。... |
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