| ObjectiveTo observe the clinical efficacy of electroacupuncture in the treatment of ischemic post-stroke depression(PSD)under the guidance of the theory of "unblocking the governor and regulating the mind",and to provide new treatment methods and ideas for the future clinical treatment of post-stroke depression.In addition,in vivo multi-channel electrophysiology,molecular biology and other techniques were used to explore the mechanism and effect of electroacupuncture,and to verify the effect of electroacupuncture on the depression phenotype of PSD rats and the possible neural mechanism.Methods1.60 patients with post-ischemic depression who met the selection criteria were randomly divided into an electroacupuncture group(30 cases)and a sham electroacupuncture group(30 cases).The acupuncture group received basic therapy combined with electroacupuncture for 4 weeks;before treatment,after the 4th week of treatment and 2 weeks after the end of treatment,the Hamilton Depression Scale(HAMD-17),the National Institutes of Health Stroke Volume Table(NIHSS score)and TCM Syndrome Depression Scale were used to evaluate the two groups of patients.Statistical analysis was performed on the scale data to evaluate the curative effect of the two groups and compare the difference in curative effect;the occurrence of adverse reactions was counted,and the evaluation and comparison between the groups were carried out.2.30 male SD rats were selected and randomly divided into 3 groups:electroacupuncture group(modeling+electroacupuncture),sham electroacupuncture group(modeling+sham electroacupuncture group),blank group(sham modeling),each group 10.Each group of rats was acclimatized and fed for 1 week.Rats in the blank group underwent sham modeling on day 1 and received 42 days of normal chow feeding.In the electroacupuncture group,after MCAO modeling was performed on the 1st day,the solitary care combined with chronic unpredictable mild stress(CUMS)modeling was performed for 21 consecutive days from the 7th day to the 28th day.Electroacupuncture was then performed for 14 consecutive days from 28 to 42 days.The rats in the sham electroacupuncture group were subjected to the solitary care combined with chronic unpredictable mild stimulation(CUMS)modeling from the 7th day to the 28th day for 21 consecutive days after the MACO modeling was performed on the 1st day.Then sham electroacupuncture was performed on days 28 to 42 for 14 consecutive days.Observe and compare whether the mental state of the rats is good,whether there is abnormal behavior,whether there is left hemiplegia(unfavorable extension of the front paw),whether the color of the body hair is normal and shiny,whether the activity is restricted,whether the diet and drinking conditions are normal,and other general states.Before R-MCAO operation,after PSD modeling and after treatment,the body weight,sugar water preference,open field test,neurological function score,and tail suspension test were evaluated and compared in each group.3.Select the SD rats after the treatment of the previous experiment.After the treatment,10 rats in each group were collected,and the brain tissue was taken out,and sliced and stained.After routine sealing,use the fluorescent confocal to observe and take pictures.Image G analysis was used to calculate the number of C-fos positive cells in the mPFC brain region within the image.4.Select 15 male SD rats,5 in each group,grouping,modeling and treatment are the same as before.After the treatment,the anesthesia machine was turned on,the rat was placed in the induction box for isoflurane gas anesthesia,and the rat was then secured to the adapter.Use scissors to cut a slit along the midline of the rat skull to expose the skull,locate the mPFC brain area according to the rat atlas,use a cranial drill to open the target area,and use the stereoscopic definition to adjust the electrode to the target area.After the target area,open the plexon software,start recording electrophysiological signals,record the data for 5 min and save.Results1.A total of 60 patients with mild-to-moderate depression after ischemic stroke who met the inclusion criteria were included in this study,and a total of 4 cases were dislodged and excluded,with a dislodgement rate of 6.67%.The electroacupuncture group and the pair of sham electroacupuncture group were evaluated before treatment,and the baseline and shedding rates of the two groups were basically the same,and the difference was not statistically significant(P>0.05),and the two groups were comparable.In this study,HAMD-17 scale scores and apparent efficiency were used as the main outcome indicators to assess the efficacy of depressive symptoms.HAMD-17 scale scores before and after treatment were compared within the group,and the differences in scores between the two groups were statistically significant(P<0.05),indicating that both electro-acupuncture and sham electro-acupuncture combined with the basal therapy had a certain degree of efficacy.Comparison between groups,the difference between the scores of the two groups was statistically significant(P<0.01),showing that the electro-acupuncture group can effectively improve the depressive symptoms of PSD patients,and it is better than the pseudo-electroacupuncture group;in terms of the total apparent efficiency,the apparent efficiency of the electro-acupuncture group was 72.41%,and the pseudo-electroacupuncture group’s efficiency was 18.52%,and the difference between the two groups in terms of the total apparent efficiency was statistically significant(P<0.01).It indicated that the electro-acupuncture group was superior to the sham electro-acupuncture group in improving the depressive symptoms of PSD patients.The TCM evidence depression scale and NIHSS scale were used as secondary outcome indicators,and it was found that the electro-acupuncture group was superior to the sham electro-acupuncture group in improving the TCM symptoms of PSD patients,and the difference was statistically significant in both cases(P<0.05).On the other hand,the efficacy of the electro-acupuncture group was comparable to that of the sham electro-acupuncture group in improving the neurological deficits of PSD patients,and the difference was not statistically significant(P>0.05).In addition,both groups of treatment programs have better safety.2.To observe the effect of electro-acupuncture on PSD rats,in terms of body weight,after 7D of R-MCAO modeling,the body weight of electro-acupuncture group and sham electro-acupuncture group decreased significantly compared with that of the blank group,and the difference was statistically significant(P<0.05).21 days after the addition of CUMS modeling,the body weight of electro-acupuncture group and sham electro-acupuncture group rose to a certain extent compared with that of the previous one but the difference between the two groups was not statistically significant(P>0.05),and compared with the blank group,the difference was statistically significant(P<0.05),The weight of the rats was increased in the electroacupuncture group compared with the sham electroacupuncture group after 14 days of electroacupuncture treatment,and the difference was statistically significant(P<0.05),indicating that PSD modeling affects the body weight of the rats and electroacupuncture is able to improve the body weight of the rats.As for the degree of neurological deficits,after 1 day of MCAO modeling,the difference in the degree of neurological deficits between the electro-acupuncture group and the sham electro-acupuncture group was statistically significant when compared with the blank group(P<0.05);after 7 and 28 days of R-MCAO modeling,the degree of neurological deficits,although partially alleviated,was statistically significant compared with that of the blank group,and the difference in the degree of the other two groups was statistically significant(P<0.05).Then,not quite as expected,after the treatment,that is,42 days after R-MCAO modeling,there was no significant difference in the degree of neurological deficits among the three groups,and although the scores of the electro-acupuncture group were lower than those of the sham group,there was no statistically significant difference(P>0.05).Regarding the degree of sugar water preference of rats,21 days after CUMS modeling,compared with the blank group,the difference in sugar water preference rate between the electro-acupuncture group and the sham electro-acupuncture group was statistically significant(P<0.05).After 14 days of electro-acupuncture treatment,the difference in sugar water preference rate between the electro-acupuncture group and the blank group was not statistically significant(P>0.05),and the difference in sugar water preference rate between the electro-acupuncture group and the sham electro-acupuncture group was statistically significant(P<0.05).As for the open field experiment,after 21 days of CUMS modeling,compared with the blank group,the differences in the horizontal movement score,the number of vertical standing and the central area activity time in the open field experiment between the electro-acupuncture group and the sham electro-acupuncture group were statistically significant(P<0.05).After 14 days of electro-acupuncture treatment,the differences in horizontal movement scores,vertical standing times and center region activity times in the electro-acupuncture group compared with the blank group in the open field experiment were not statistically significant(P>0.05),and the differences in horizontal movement scores,vertical standing times and center region activity times in the electro-acupuncture group compared with the sham electro-acupuncture group were statistically significant(P<0.05).As for the tail suspension experiment,after 21 days of CUMS modeling,the difference in immobility time of tail suspension test between electro-acupuncture group and sham electro-acupuncture group were all statistically significant(P<0.05)compared with the blank group.After 14 days of electro-acupuncture treatment,there was no statistically significant difference in the immobility time of the suspended tail test between the electro-acupuncture group and the blank group(P>0.05),and the difference in the immobility time of the suspended tail test between the electro-acupuncture group and the sham electro-acupuncture group was statistically significant(P<0.05).3.To observe the effect of electro-acupuncture,the number of C-fos-positive cells in the mPFC brain region was observed by using immunofluorescence technique.It was found that the number of C-fos positive cells in the electro-acupuncture group was significantly increased when compared with the blank and sham electro-acupuncture groups,and the difference was statistically significant(P<0.05).The changes of excitation neurons and inhibitory neurons in the mPFC brain region were further observed by in vivo multichannel electrophysiology.The results showed that relative to the blank group,the modeling group exhibited a decrease in the excitability of inhibitory interneurons and an increase in the excitability of excitatory vertebral neurons,whereas electro-acupuncture could reverse this pathological change,with a statistically significant difference(P<0.05).Conclusion1.In the treatment of depression symptoms in patients with PSD,the Tongdutiaoshen acupuncture method is superior to sham electro-acupuncture,which confirms the significant advantage of the characteristic theory of Tongdutiaoshen acupuncture method in the treatment of PSD,and is worthy of widespread clinical promotion;There is a lack of evidence-based evidence for its efficacy,and more large-sample clinical trials are needed to verify it.2.The depression phenotype of the PSD rat model prepared by R-MCAO+CUMS combined with solitary rearing is stable and reliable;and electroacupuncture can effectively improve the depressive symptoms of ischemic PSD rats.3.Electroacupuncture can effectively activate the neurons in the mPFC brain area;at the same time,electroacupuncture can improve the depression phenotype of PSD rats by regulating the balance of excitability and inhibition of neurons in the mPFC brain area,which may be the effect of electroacupuncture in the treatment of PSD.One of the mechanisms of depressive symptoms. |