Research Progress in the Treatment of Poststroke Depression with Traditional Chinese Medicine

In recent years,the incidence rate of stroke has increased year by year.Post stroke depres‐sion is one of its main complications,which seriously affects the recovery of physiological functions and quality of life of stroke patients.Traditional Chinese medicine has signifi‐cant therapeutic effects in treating this disease.This article provides a classification and review of traditional Chinese medicine treatment methods for post-stroke depression,and looks forward to the current problems.

miR-137, a new target for post-stroke depression?

Expression of miR-137 is downregulated in brain tissue from patients with depression and suicidal behavior, and is also downregulated in peripheral blood from stroke patients. However, it is not yet known if miR-137 acts as a bridge between stroke and depression. To test this, we used middle cerebral artery occlusion and chronic mild stress to establish a post-stroke depression model in rats. Compared with controls, we found significantly lower miR-137 levels in the brain and peripheral blood from post-stroke depression rats. Injection of a miR-137 antagonist into the brain ventricles upregulated miR-137 levels, and improved behavioral changes in post-stroke depression rats. Luciferase assays showed miR-137 bound to the 3＇UTR of Grin2A, regulating Grin2A expression in a neuronal cell line. Grin2A gene overexpression in the brain of post-stroke depression rats, no- ticeably suppressed the inhibitory effect of miR-137 on post-stroke depression. Overall, our results show that miR-137 suppresses Grin2A protein expression through binding to Grin2A mRNA, thereby exerting an inhibitory effect on post-stroke depression. Our results offer a new therapeutic direction for post-stroke depression.

The effects of Xingnao Jieyu capsules on post-stroke depression are similar to those of fluoxetine

The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in the present study, we established a rat model of post-stroke depression using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats received intragastric perfusion with 0.82, 0.41, and 0.20 g/kg Xingnao Jieyu capsules separately dissolved in 2 mL distilled water. Fluoxetine served as a positive control. The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results demonstrated that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depression. These therapeutic effects were similar to those of fluoxetine. These results indicate that Xingnao Jieyu capsules upregulate synaptotagmin expression in hip pocampi of rats with post-stroke depression, and exert antidepressant effects.

Electroacupuncture at the Wangu (GB 12) acupoint suppresses expression of inflammatory factors in the hippocampus and frontal lobe of rats with post-stroke depression

Electroacupuncture was performed at the Wangu （GB 12） acupoint, whose position is similar to the cerebellar fastigial nucleus in rats with post-stroke depression. Results showed that the expression of nuclear factor-κB and the levels of tumor necrosis factor-α and interleukin-1β decreased. Simultaneously, the extent of edema in the hippocampus and frontal lobe decreased, and the morphology of the nerve cells recovered to near normal. In addition, fluoxetine treatment displayed a similar effect on post-stroke depression as electroacupuncture at GB 12 acupoint. The results indicate that electroacupuncture at GB 12 acupoint can reduce the levels of cytokines in the hippocampus and frontal lobe of rats with post-stroke depression, and thus provide a neuroprotective effect on post-stroke depression.

Apolipoprotein E polymorphisms increase the risk of post-stroke depression

Recent reports have shown that apolipoprotein E （APOE） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOE affects post-stroke depression. Accordingly, we hypothesized that APOE polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOE rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOE genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOE rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOE rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.

Metabolic changes of prefrontal cerebral lobe,white matter and cerebellum in patients with post-stroke depression A proton magnetic resonance spectroscopy study

BACKGROUND： Proton magnetic resonance spectroscopy （IH-MRS） non-invasively detects changes in chemical substances in the brain, which reflects the pathological metabolism.OBJECTIVE： To investigate changes in N-acetyl-aspartate （NAA）, choline （Cho）, creatine （Cr）, and myoinositol （MI） in the gray and white matter of cerebral prefrontal lobe and cerebellum of patients with differential degrees of post-stroke depression （PSD） using ^1H-MRS. DESIGN： A case control study. SETTING： The First Affiliated Hospital of the Dalian Medical University. PARTICIPANTS： A total of 38 patients with stroke （28 male and l0 female patients, aged 40 to 79 years） were selected from the Department of Neurology, 1st Affiliated Hospital, Dalian Medical University, from February to October in 2004. All subjects met the DSM-IV criteria for cerebrovascular disease and depression. The degree of depression was defined according to Hamilton criteria. 38 patients with PSD were divided into two groups according to the time after ischemia, 20 patients in the acute group with less than 10 days after ischemic attack （mild： 16 patients, moderate/severe： 4 patients） and 18 patients in the chronic group with more than l l days after ischemic attack （mild： 15 patients, moderate/severe： 3 patients）. Seventeen healthy volunteers with matching age from 41 to 80 years were examined as a control group. The study was approved by the Medical Ethics Committee of the University Medical Center Utrecht, and each participant signed an informed consent form. METHODS： Spectra were acquired by multi-voxel point-resolved spectroscopy （PRESS） sequence with GE signal.5T MR/i, localized in prefrontal cerebral lobe and cerebellum. Values of NAA, Cho, MI, and Cr ere compared between different graded PSD patients and control subjects with one-way analysis of variance in software SPSS 11.5. MAIN OUTCOME MEASURES： Metabolite concentration in different brain regions of interest. Difference in metabolites between distinctly graded PSD patients and control subjects. Exclusion of age-effects on metabolites. RESULTS： Metabolite concentrations of different brain regions： A significant rise in the Cho/Cr ratio was detected in the acute and chronic group compared to the control group. The ratio change was more significant in the acute group （P 〈 0.05）. There was no significant difference between these three groups for other metabolites detected by IH-MRS in the right frontal white matter, bilateral frontal grey matter, and cerebellum （P 〉 0.05）. Comparison of metabolite levels among differently graded PSD patients and control subjects： a significant increase in the Cho/Cr ratio was detected in the left frontal white matter compared to the control group （P 〈 0.05）. There was no significant difference in age between patients in the stroke groups and the control group （P 〉 0.05）, and similarly, there was no significant correlation between age and absolute or relative values in the control group （P 〉 0.05）. CONCLUSION： Abnormalities of frontal lobe in PSD were located in the white matter. There was early abnormality of metabolic substance in PSD.

CLINICAL STUDY ON ACUPUNCTURE IN THE TREATMENT OF POST-STROKE DEPRESSION WITH THE METHOD OF ACTIVATING THE DU MERIDIAN AND CLEARING THE MIND

Objective: To observe the therapeutic effect of acupuncture in the treatment of post-stroke depression (PSD) with the method of activating the Du Meridian and clearing the mind. Methods: Two hundred and thirty one cases of PSD were randomly divided into two groups, acupuncture and control groups. In acupuncture group, Baihui (百会 GV 20), Dazhui (大椎 GV 14), Neiguan (内关 PC 6), Taichong (太冲 LR 3) and Shenmen (神门 HT 7) were selected as the main points to invigorate flow of qi in the Du Meridian and clear the mind. Patients in the control group received Fluoxetine orally, 20 mg once per-day. In addition, the same routine treatments were given to both groups, strengthened with rehabilitation exercises as early as possible; 8 weeks constituted one therapeutic course. HAMD and severity of neuro-functional defect of each case were evaluated before and 8-week after the treatment. Results: The total effective rate of acupuncture group was 92.37%, the control group, 72.88%. According to χ2 test, the difference between the two groups was remarkably significant (P<0.05). Conclusion: Acupuncture therapy of activating the Du Meridian and clearing the mind in the treatment of PSD was safe and effective.

Role of Transcranial Direct Current Stimulation in the Management of Post-Stroke Depression

Study Objectives: Stroke is a major neurological disease significantly threatening the human health and life with a high morbidity, disability, and mortality. Post-stroke depression (PSD) is one of the common complications of stroke. PSD has been a major factor hindering the recovery of neurological functions and daily activities in stroke patients and is closely related to the social avoidance and increased mortality of stroke patients. Although antidepressant drug treatment has improved during the last decades, symptoms in about 20% of the patients are not in remission two years after initiation of pharmacological intervention. Nowadays, non-invasive brain stimulation;techniques;transcranial direct current stimulation (tCDS) has gained an important interest in the treatment of many neuropsychiatric disorders which might be of some help in treatment of PSD. The goal of the current study is to evaluate the beneficial short term role of tDCS on post-stroke depression. Study Design: This was a randomized double blind placebo-controlled clinical trial included forty hemiparetic patients with post-stroke depression from outpatient clinic of Faculty of Physical Therapy, Cairo University, in the period between June 2018 to June 2019. All patients diagnosed as having a PSD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Depression was evaluated by Hamilton Depression Rating Scale (HAM-D) pre and post treatment and quality of life was evaluated by the Stroke Specific Quality Of Life scale (SS-QOL). Patients were assigned randomly into two groups: the study group A and the control group B. Both groups received antidepressant medication in addition to physical therapy program. Group A received tCDS for 30 minutes, three times per week for one month, while the group B received sham transcranial direct current stimulation. Results: Active tDCS was significantly superior to sham with significant improvement in depression and Stroke Specific Quality Of Life in treated group in comparison to group B, p = 0.000. Conclusion: tDCS was effective for post- stroke depression and might be a favorable option for treating post-stroke patients.

Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(银杏蜜环口服溶液) attenuates inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis in post stroke depression

OBJECTIVE The Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(Yinxingmihuan Koufu Rongye,YXMH),a representative drug for"Treating both Brain and Heart",showed considerable clinical effects in isch⁃emic cardiovascular and cerebral vascular diseases.Recently,it is reported that YXMH has the potential for treating myocardial and cerebral ischemia related mental disorders,such as post stroke depression(PSD)and chronic heart disease(CHD)associated anxiety disorder.However,its mechanism has not been clearly elucidated.Meanwhile,increasing evidence revealed that there are close functional links between depression and habenular nucleus.The present study investigates the underlying mechanism of YXMH on attenuating the inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis in in a rat model of PSD.METHODS Rats were randomly devided into sham group,model group,Ginaton group(18 mg·kg^-1),Armillariella Mellea group(600 mg·kg-1),Fluoxetine group(10 mg·kg^-1),YXMH high-dose group(618 mg·kg^-1)and YXMH low-dose group(309 mg·kg^-1).The PSD model was induced by transarterial microembolization combined with sleep deprivation(2-Chloro-D-phenylalanine,PCPA,IH,200 mg·kg^-1,for 3 times,before the behavior test)in SD male rats.Then rats were treated with corresponding medicaments through gavage once a day until 3 weeks later,followed by body mass measurement,neurological deficit score evaluation,gripping strength and thermal withdrawl latency measurement,as well as depression related behavioral indicators,the open field test(OFT)and sucrose preference test.The pathological morphological changes of habenular nucleus was observed by HE staining,the expression of IBA-1 was measured and analyzed by immunohistochemistry staining,and alterations of proteins and genes related to the CX3CL1-CX3CR1 axis were analyzed using Western blotting(CX3CL1,CX3CR1)and real-time polymerase chain reaction(PCR)(CX3CL1,CX3CR1).RESULTS Compared with the sham group,rats in the model group manifested as decreased body mass,deficient neurological behavior and gripping strength,reduced loco⁃motor activity and sugar water consumption,as well as elevated thermal withdrawl latency(P<0.05,P<0.01).Mean⁃while,the pathological morphology of the habenular nucleus on the ischemic hemisphere showed significant neuronal degeneration,microglial proliferation,inflammatory cells and glia cells infiltration,together with up-regualted expression of IBA-1,CX3CL1,CX3CR1 protein and CX3CL1,CX3CR1 mRNA.YXMH attenuated inflammation of microglia in habenular nucleus through improving pathological morphology,inhibiting IBA-1 activation,down-regulating the expres⁃sion of CX3CL1 and CX3CR1 proteins and genes,and thus improved the behavior performance of ischemic injury and depression.CONCLUSION YXMH ameliorates neurological deficit and depressive behavior in rat model of PSD induced by transarterial microembolization combined with sleep deprivation,and the mechanism is probably related to attenu⁃ating inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis.

Sociodemographic profile and social support for post-stroke depression in Kinshasa: A rehabilitation based cross-sectional study

The World Health Organization has highlighted the emergence of non-communicable chronic diseases, including stroke, in developing countries. As a cause of death, stroke ranks first in Africa. Stroke is the foremost cause of neuropsychiatric disease, including post-stroke depression (PSD) which is a very common disease. Surveys of this condition in Congolese pa tients are virtually non-existent. The objectives of this study were to assess the prevalence of PSD in Congolese patients and identify associated sociodemographic factors. Age, sex, address, province of origin, social and professional status, education, religion and consumption habits were chosen as indicators or parameters of interest to be examined in this study. The results of descriptive analyses are presented as frequencies for categorical variables and as mean ± standard deviation for quantitative variables. The association between different variables was assessed using tables of comparisons of proportions and the Chi-square test. Logistic regression was performed to predict the occurrence of PSD. There were more male than female patients. The mean age was 54.67 ± 12.51 years. Nearly 3 fourths of the patients were aged less than 65. The family was the primary source of social support. The majority was satisfied by the social support received from the family. Just over half the study patients (53.6%) had mild to severe depression as assessed by the PHQ9. Univariate analysis and logistic regression indicated a statistically significant association between low educational level and the occurrence of PSD. However, there was no relationship between age, sex or drinking habits and the onset of PSD. The majority of the subjects were satisfied by the social support from their families. Depression was common after stroke with the occurrence of 53.6%. These results highlight the need to investigate, diagnose and treat PSD, which is a risk factor for morbidity and mortality after stroke.

Melatoninergic Antidepressant in Post-Stroke Depression Therapy

This paper presents the results of the effects of Melitor (25 mg during two months) on the psychic-emotional state, cerebral hemodynamic and bioelectrical activity of the brain in 30 patients (average age 66.2 ± 3.2 years) with ischemic post-stroke depression. It has been found that this drug possesses a multimodal action which is characterized by the decrease of the level of depression, widening of the range of social-environmental activity, improvement of the cerebral blood circulation and harmonization of the brain electrogenesis. In the patients with right versus left hemisphere stroke, the effect of Melitor on the functional state of the brain was more pronounced. Based on the results obtained in our study, we can recommend Melitor to use it in complex scheme of rehabilitation care of patients of the given nosological category.

Predictive power of abnormal electroencephalogram for post-cerebral infarction depression

Electroencephalography is a sensitive indicator for measuring brain condition, and can reflect early changes in brain function and severity of cerebral ischemia. However, it is not yet known whether electroencephalography can predict development of post-cerebral infarc- tion depression. A total of 321 patients with ischemic stroke underwent electroencephalography and Hamilton Depression Rating Scale assessment to analyze the relationship between electroencephalography and post-cerebral infarction depression. Our results show that electroencephalograms of ischemic stroke patients with depression exhibit low-amplitude alpha activity and slow theta activity. In con- trast, electroencephalograms of ischemic stroke patients without depression show fast beta activity and slow delta activity. ＂Ihese findings confirm that low-amplitude alpha activity and slow theta activity can be considered as independent predictors for post-cerebral infarction depression.

小续命汤合百合地黄汤治疗卒中后抑郁(PSD)忧郁伤神证的GC-MS研究

目的探讨卒中后抑郁(PSD)忧郁伤神症患者给予小续命汤合百合地黄汤治疗的气相色谱-质谱联用(GCMS)分析结果。方法选取2018年12月至2019年12月南阳张仲景医院收治的60例PSD忧郁伤神症患者,按照随机数字表法分成研究组(30例)与对照组(30例),对照组给予氟哌噻吨美利曲辛片治疗,研究组给予小续命汤合百合地黄汤治疗,比较两组临床疗效、抑郁情绪、血清代谢组学及神经功能。结果研究组治疗有效率(93.33%)高于对照组(70.00%);治疗后两组汉密尔顿抑郁量表(HAMD)评分低于治疗前,且研究组低于对照组;治疗后,两组谷氨酰胺(Gln)、谷氨酸(Glu)、胍基乙酸(GAA)表达强度小于治疗前,且研究组小于对照组;治疗后两组美国国立卫生研究所卒中量表(NIHSS)评分低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05)。结论PSD忧郁伤神症患者给予小续命汤合百合地黄汤治疗,能够提升临床疗效,减轻抑郁情绪,调节血清代谢组学,改善患者神经功能。

Anti-depressant effects of Jieyu Anshen granule in chronic unpredictable mild stress-treated rats after ischemic stroke

OBJECTIVE To explore the effects and underlying mechanism of Jieyu Anshen granule(JY) in chronic unpredictable mild stress(CUMS)-treated rats after ischemic stroke.METHODS A rat model of post-stroke depression(PSD) was developed by additional CUMS procedures after middle cere.bral artery occlusion(MCAO).Sprague-Dawley rats were given 1 g·kg^(-1) and 3 g·kg^(-1) of JY by gastrogavage for 4 weeks.Escitalopram(10 mg·kg^(-1)) served as a reference drug.Behavioral tests including sucrose preference test,forced swim test and open-field test were performed to evaluate the antidepressant effects.Levels of norepinephrine(NE),dopamine(DA) and 5-hydroxytryptamine(5-HT) in rat brain were assayed.The anti-inflammatory activity was evaluated by measuring TNF-α and IL-1β in brain.Serum adrenocorticotropic hormone(ACTH) and corticosterone(CORT) were estimated as indices of hypothalamic-pituitary-adrenal(HPA) axis activity.Western blot analysis was used to evaluate hippo.campal expression of the 5-HT1 A receptor(5-HT_(1A)R) and brain-derived neurotrophic factor(BDNF).RESULTS PSD rats exhibited decreased sucrose consumption and motor activity,increased immobility time(P<0.01).JY treatment reversed the depressive behaviors in PSD rats(P<0.05,P<0.01).Treat.ment with JY resulted in significantly increased levels of NE,DA and 5-HT in the hippocampus and prefrontal cortex(P<0.05,P<0.01),and increased expression of 5-HT_(1A)R and BDNF in the hippocampus(P<0.01).JY treatment significantly down-regulated the levels of TNF-α and IL-1β in hippocampus and prefrontal cortex(P<0.05).Treatment with JY also resulted in significantly decreased ACTH and CORT in serum which had been increased(P<0.05).CONCLUSION These findings suggest that JY treat.ment could ameliorate PSD,and the effects are likely ascribed to inhibiting HPA axis hyperfunction and inflammatory,up-regulating the levels of neurotransmitters(NE,DA and 5-HT),and the expression of hippocampal 5-HT_(1A)R and BDNF.

脑梗死患者康复科住院期间卒中后抑郁程度的相关因素

目的 探讨脑梗死患者在康复科住院期间发生卒中后抑郁的相关危险因素。方法 回顾性分析2019年12月至2023年2月在北京博爱医院住院、曾诊断为抑郁状态且经心理科会诊的脑梗死患者,统计一般资料(性别、年龄、学历、婚姻),疾病特征(病程、病灶位置、偏瘫侧别、感觉障碍、失语、失眠、吞咽障碍、肩手综合征、便秘),运动功能(偏瘫侧肌力、Brunnstrom分期),简易精神状态检查(MMSE)、美国国立卫生研究院卒中量表(NIHSS)、Fugl-Meyer评定量表(FMA)、Fugl-Meyer评定量表-平衡(FMA-B)、改良Barthel指数(MBI)、汉密尔顿抑郁量表(HAMD)评分等资料。HAMD≤20分的患者入低HAMD组,HAMD> 20分的患者入高HAMD组。结果 在2 403例脑梗死患者中,诊断为抑郁状态且经心理科会诊的患者269例,低HAMD组103例,高HAMD组166例。高HAMD组便秘发生率较低,吞咽障碍、肩手综合征发生率较高(χ^(2)> 5.379, P <0.05);髂腰肌、股四头肌肌力,下肢和手Brunnstrom分期,NIHSS、MMSE、FMA、FMA-B、MBI评分差于低HAMD组(|Z|> 2.020, t> 2.171, P <0.05)。Logistic回归分析显示,便秘(OR=0.435)、股四头肌肌力(OR=0.782)、吞咽障碍(OR=2.602)是康复期患者发生卒中后抑郁的相关因素(P <0.05)。结论 卒中后吞咽障碍和肌力下降,可能加重卒中后抑郁。便秘可能并不加重卒中后抑郁程度。

白细胞介素10和过氧化氢酶对急性缺血性卒中病人卒中后抑郁的预测价值

目的:探讨白细胞介素10(IL-10)和过氧化氢酶(CAT)对急性缺血性卒中病人卒中后抑郁(PSD)的预测价值。方法:151例急性缺血性卒中病人入院后24 h内测定血清IL-10、CAT水平。使用17项汉密尔顿抑郁量表(HAMD-17)来评估抑郁症状;PSD定义为HAMD评分≥8。结果:脑梗死后1个月开始随访,有51例(33.8%)被诊断为PSD。与非PSD病人相比,PSD组入院和出院时NIHSS评分较高,脑梗死体积较大,BI评分较低,mRS评分较高,血清CAT、IL-10水平较低(P<0.05)。在调整了潜在混杂因素(在单变量逻辑回归分析中,P<0.05)后,IL-10(OR=0.615,95%CI:0.410~0.923)和CAT(OR=0.757,95%CI:0.652~0.914)仍然是PSD的独立预测因子。PSD病人的IL-10水平(r=0.394,P<0.01)和CAT水平(r=0.306,P<0.01)与HAMD评分呈负相关。ROC分析显示,血清IL-10水平的截止点为2.06 pg/mL,预测PSD的AUC为0.739。同时,CAT水平的截止点为1.07 U/L,预测PSD的AUC为0.630。IL-10水平较低(<2.06 pg/mL)的病人比对应组(≥2.06 pg/mL)更容易发生PSD(OR=9.750,95%CI=2.671~35.534,P<0.01)。同样,CAT水平较低(<1.07 U/L)的病人比对应组(≥1.07 U/L)更容易发生PSD(OR=5.052,95%CI=1.256~20.322,P<0.05)。结论:血清IL-10、CAT可用作急性缺血性卒中病人PSD的独立保护性预测因子。IL-10、CAT水平低的病人在卒中后1个月更有可能发生PSD。

丹栀逍遥散联合和调督任安神针刺法对卒中后抑郁患者的临床疗效

目的探讨丹栀逍遥散联合和调督任安神针刺法对卒中后抑郁患者的临床疗效。方法98例患者随机分为对照组和观察组,每组49例,对照组给予常规治疗,观察组在对照组基础上加用丹栀逍遥散联合和调督任安神针刺法,疗程4周。检测临床疗效、MoCA评分、肠道菌群(肠球菌、乳酸杆菌、大肠埃希菌、双歧杆菌)、免疫功能指标(IgM、IgG、IgA)、抑郁状态指标(HAMD评分、SDS评分)、不良反应发生率变化。结果观察组总有效率高于对照组(P<0.05)。治疗后,2组MoCA评分、免疫功能指标升高(P<0.05),HAMD评分、SDS评分降低(P<0.05),肠球菌、大肠埃希菌减少(P<0.05),乳酸杆菌、双歧杆菌增加(P<0.05),以观察组更明显(P<0.05)。2组不良反应发生率比较,差异无统计学意义(P>0.05)。结论丹栀逍遥散联合和调督任安神针刺法可安全有效地改善卒中后抑郁患者认知功能和体液免疫,调节肠道菌群,减轻抑郁症状。

神经复元方对H_(2)O_(2)诱导的大鼠海马神经元损伤后雄激素受体活化的影响

[目的]探究神经复元方对过氧化氢(H_(2)O_(2))诱导的SD大鼠海马神经元损伤中雄激素受体(AR)的活化影响,探讨其治疗卒中后抑郁的作用机制。[方法]取新生24 h的SD大鼠的海马组织,分离原代大鼠海马神经元,通过微管相关蛋白2(MAP-2)免疫荧光鉴定细胞。对SD大鼠给予神经复元方灌胃处理,分离血清,获得空白血清和含药血清,再利用细胞计数试剂(CCK8)检测确定含药血清的最佳处理浓度。使用100μmol/L的H_(2)O_(2)对大鼠海马神经元细胞处理致损伤,分为空白血清组、损伤模型+空白血清组、损伤模型+含药血清组、损伤模型+氟西汀4组。利用蛋白质免疫印迹法(Western blot)和免疫荧光检测各组AR蛋白磷酸化及非磷酸化的情况。[结果]与空白血清组相比,损伤模型+空白血清组的AR、p-AR蛋白表达显著下降。与损伤模型+空白血清组相比,损伤模型+含药血清组和损伤模型+氟西汀组的AR、p-AR蛋白表达上升。[结论]神经复元方对H_(2)O_(2)诱导的SD大鼠海马神经元损伤有一定修复作用,能够促进AR活化,提示AR可能为神经复元方治疗脑卒中后抑郁的重要靶蛋白。

基于网络药理学、分子对接和动物实验探究柴胡龙骨牡蛎合甘麦大枣汤治疗脑卒中后抑郁的作用机制

目的:基于网络药理学、分子对接与动物实验探究柴胡龙骨牡蛎合甘麦大枣汤治疗脑卒中后抑郁(PSD)的作用机制。方法:利用TCMSP等数据库预测柴胡龙骨牡蛎合甘麦大枣汤的活性成分及靶点;在PharmGKB等数据库检索PSD疾病靶点,利用Cytoscape(v 3.9.1)建立交集靶点网络,String(v11.5)数据库构建PPI网络,利用DAVID 6.8数据库进行GO富集及KEGG通路分析;运用AutoDock vina(v 1.1.2)软件进行分子对接,并使用Pymol(v 2.5)等软件进行可视化分析;动物实验设置空白组、模型组、盐酸氟西汀组、中药组、中药+盐酸氟西汀组,给药21 d后检测各组大鼠神经行为学评分、脑组织内神经递质以及炎症因子表达,RT-qPCR和Western blot检测关键基因PPARG、MAPK3、AKT1、PIK3CA mRNA及蛋白表达。结果:得到柴胡龙骨牡蛎合甘麦大枣汤活性成分225种,作用于PSD的靶点119个,关键靶点包括MAPK3、AKT1、PIK3CA、PPARG,关键通路包括MAPK信号通路、PI3K-Akt信号通路等。与模型组比较,中药组与中药+盐酸氟西汀组MAPK3 mRNA及蛋白表达降低,AKT1、PIK3CA、PPARG mRNA及蛋白表达升高(P<0.05)。结论:柴胡龙骨牡蛎合甘麦大枣汤治疗PSD的作用机制可能与抑制MAPK3表达、促进AKT1、PIK3CA、PPARG表达,减缓脑组织炎症反应和氧化应激有关。

柴胡疏肝散合半夏厚朴汤联合五行针灸对脑卒中后焦虑抑郁的神经调控作用及对免疫炎症反应、认知功能损害和HPG、HPT的影响

目的:观察柴胡疏肝散合半夏厚朴汤联合五行针灸对脑卒中后焦虑抑郁患者的神经调控作用及对免疫炎症反应、认知功能损害和下丘脑-垂体-性腺轴(HPG)、下丘脑-垂体-甲状腺轴(HPT)的影响。方法:选择2021年3月至2023年5月于该院治疗的脑卒中后焦虑抑郁患者102例,根据随机数字表法分组,其中五行针灸组51例(脱落2例,最终纳入49例),方剂联合组51例(脱落2例,最终纳入49例)。两组患者同时给予常规西医基础治疗,五行针灸组患者在常规西医基础治疗的基础上给予五行针灸治疗,方剂联合组患者在五行针灸组的基础上给予柴胡疏肝散合半夏厚朴汤治疗。观察两组患者的临床疗效,比较患者治疗前后的中医证候评分、简易精神状态量表(MMSE)评分、广泛性焦虑障碍量表(GAD-7)评分、汉密顿抑郁量表(HAMD)评分和简明幸福与生活质量满意度问卷(Q-LES-Q-SF)评分,检测患者治疗前后血清神经生长因子(NGF)、白细胞介素1β(IL-1β)、胶质纤维酸性蛋白(GFAP)、白细胞介素17a(IL-17a)、促甲状腺激素(TSH)、5-羟色胺(5-HT)和雌二醇(E2)水平。结果:方剂联合组患者的总有效率为97.96%(48/49),高于五行针灸组的81.63%(40/49),差异有统计学意义(P<0.05)。治疗后,方剂联合组患者精神焦虑抑郁、脘痞、胸胁作胀、善太息和嗳气频作等中医证候评分较五行针灸组降低,HAMD、GAD-7评分较五行针灸组降低,MMSE、Q-LES-Q-SF评分较五行针灸组升高,差异均有统计学意义(P<0.05)。治疗后,方剂联合组患者的IL-1β、IL-17a和GFAP水平较五行针灸组降低,NGF水平较五行针灸组升高,5-HT、E2和TSH水平较五行针灸组升高,差异均有统计学意义(P<0.05)。结论:柴胡疏肝散合半夏厚朴汤联合五行针灸治疗脑卒中后焦虑抑郁患者,可减少免疫炎症反应,减少神经及认知功能损害,调节HPG、HPT,改善焦虑及抑郁情绪,缓解病情,提高生活质量及临床疗效。