Antidepressant effects of Peiyuan Jieyu formula in a mouse model of chronic stress in conjunction with lipopolysaccharide-induced depression

Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.

Zuogui Jiangtang Jieyu Formula ameliorating hippocampal neuronal apoptosis in diabetic rats with depression by inhibiting JNK signaling pathway

Objective To investigate the effect of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZJJF)on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway.Methods(i)A total of 72 specific pathogen-free(SPF)grade male Sprague Dawley(SD)rats were randomly divided into six groups,with 12 rats in each group:control,model,metformin(Met,0.18 g/kg)+fluoxetine(Flu,1.8 mg/kg),and the high-,medium-,and low-ZJJF dosages(ZJJF-H,20.52 g/kg;ZJJF-M,10.26 g/kg;ZJJF-L,5.13 g/kg)groups.All groups except control group were injected once via the tail vein with streptozotocin(STZ,38 mg/kg)combined with 28 d of chronic unpredictable mild stress(CUMS)to establish diabetic rat models with depression.During the CUMS modeling period,treatments were administered via gavage,with control and model groups receiving an equivalent volume of distilled water for 28 d.The efficacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose,insulin,and glycated hemoglobin levels,along with behavioral assessments,including the open field test(OFT),forced swim test(FST),and sucrose preference test(SPT).Hippocampal tissue damage and neuronal apoptosis were evaluated using hematoxylin-eosin(HE)staining and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling(TUNEL)staining.Apoptosis-related proteins Bax,Bcl-2,caspase-3,and the expression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).(ii)To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological effects of ZJJF,an additional 50 SPF grade male SD rats were randomly divided into five groups,with 10 rats in each group:control,model,SP600125(SP6,a JNK antagonist,10 mg/kg),ZJJF(20.52 g/kg),and ZJJF(20.52 g/kg)+Anisomycin(Aniso,a JNK agonist,15 mg/kg)groups.Except for control group,all groups were established as diabetic rat models with depression,and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period.Behavioral changes in rats were evaluated through the OFT,FST,and SPT,and hippocampal neuron damage and apoptosis were observed using HE staining,Nissl staining,TUNEL staining,and transmission electron microscopy(TEM).Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed.

A network pharmacology approach to decipher the mechanisms of anti-depression of Xiaoyaosan formula

OBJECTIVE Depression is one of the prevalent and prominent complex psychiatric diseases and the number of depressed patients has been on the rise globally during the recent decades.Xiaoyaosan,as a famous Chinese herbal formula,has been widely used in depression patients for a long time. However,the therapeutic mechanisms remain uncertain because of difficulty of depression pathophysiology and the lack of bioinformatic approach to understand the molecular connection. METHODS In this thesis,we applied a network pharmacology approach to explain the potential mechanisms between Xiaoyaosan and depression involved in oral bioavailability screening,drug-likeness assessment,caco-2 permeability,blood-brain barrier target recognition and network analysis. RESULTS 66 active compounds in Xiaoyaosan formula with favorable pharmacokinetic profiles are predicted as active compounds for anti-depression treatment. Network analyses show that these 66 compounds target 40depression-associated proteins including especially HTR2A,NR 3C1,MAOB,XDH and CNR2. These proteins are mainly involved in the neuroactive ligand-receptor interaction,serotonergic synapse,cAMP signaling pathways and calcium signaling pathways. CONCLUSION The integrated network pharmacology method is an effective approach to illustrate the anti-depression mechanisms of herbs,and this in silico approach can be applied in drug discovery.

Protective effects of Zuogui Jiangtang Jieyu Formula on hippocampal neurons in rats of diabetes complicated with depression via the TRP/KYN metabolic pathway

Objective To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZGJTJYF)on hippocampal neurons in rats of diabetes complicated with depression(DD)via the TRP/KYN metabolic pathway.Methods(i)In vivo experiments:60 specified pathogen free(SPF)grade male Sprague-Dawley(SD)rats were randomly divided into six groups with 10 rats in each groups:control,DD model,positive(1.8 mg/kg fluoxetine+0.18 g/kg metformin),high-dose ZGJTJYF(ZGJTJYFH,40.500 g/kg ZGJTJYF),middle-dose ZGJTJYF(ZGJTJYF-M,20.250 g/kg ZGJTJYF),and lowdose ZGJTJYF(ZGJTJYF-L,10.125 g/kg ZGJTJYF)groups.Except for the control group,other groups were established DD model by high-fat emulsion intake with single tail vein streptozotocin(STZ)and four weeks of chronic unpredictable mild stress(CUMS).All drug administration groups were treated by gavage during CUMS modeling,and the control and model groups were given equal amount of distilled water.After four weeks,the serum levels of blood glucose and glycosylated hemoglobin were measured to determine the hypoglycemic effect of ZGJTJYF.Moreover,the open field test and Morris water maze test were performed to evaluate the antidepressant effect of ZGJTJYF.Changes in 5-hydroxytryptamine(5-HT)level were detected via high-performance liquid chromatography with electrochemical detection(HPLC-ECD);the levels of tryptophan(TRP),kynurenine(KYN),and indoleamine 2,3-dioxygenase(IDO)in the hippocampus were detected using enzyme-linked immunosorbent assay(ELISA);the protein expression levels of synaptophysin(SYN)and postsynaptic density material-95(PSD-95)were detected via immunohistochemistry(IHC);and the protein expression levels of N-methyl-D-aspartate receptor(NR)2 A and NR2 B were detected using Western blot.(ii)In vitro experiments:five SPF grade SD pregnant rats(E16–18)were used to obtain primary hippocampal neurons(Ne),six SD new-born rats were used to collected primary astrocytes(As)and microglia(MG),and to establish a Ne-As-MG co-culture system.All co-culture systems were divided into six groups:control(PBS),model[150 mmol/L glucose+200μmol/L corticosterone(G&P)+PBS],blank(G&P+blank serum),positive(G&P+positive drug-containing serum),ZGJTJYF(G&P+ZGJTJYF serum),and 1-methyl-D-tryptophan(1-MT,IDO inhibitor)(G&P+1-MT)groups.After 18 h of intervention by corresponding treatment,immunofluorescence was used to analyze the protein expression levels of SYN,PSD-95,NR2 A,and NR2 B;ELISA was performed to measure the levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,and TRP/KYN metabolic pathway-related factors[TRP,KYN,kynurenine acid(KYNA),quinolinic acid(QUIN)].Results(i)In vivo experimental results showed that ZGJTJYF-M and ZGJTJYF-L significantly improved the elevated blood glucose state of DD rats(P<0.01 and P<0.05,respectively);ZGJTJYF-H,ZGJTJYF-M,and ZGJTJYF-L increased their autonomous activity,learning,and memory ability(P<0.01,P<0.01,and P<0.05,respectively).Moreover,the levels of 5-HT and TRP were significantly increased(P<0.01),and the levels of KYN and IDO were significantly decreased in the hippocampus(P<0.01)of rats after ZGJTJYF-M treatment.The protein expression levels of SYN and PSD-95 were significantly upregulated in hippocampal neurons(P<0.01),while the abnormal activation of NR2A and NR2B was markedly inhibited in hippocampus(P<0.05)of rats after ZGJTJYF-M treatment.(ii)In vitro experimental results showed that ZGJTJYF-containing serum significantly increased the protein expression levels of SYN and PSD-95 in hippocampal neurons(P<0.01),decreased the levels of IL-1β(P<0.01),IL-6(P<0.05),TNF-α(P<0.01),IDO(P<0.05),KYN(P<0.05),and QUIN(P<0.01),and increased the levels of TRP and KYNA(P<0.01)in the simulated DD state.ZGJTJYF also had an significantly inhibitory effect on the abnormal activation of NR2A and NR2B in neurons(P<0.05)in a stimulated DD state.Conclusion ZGJTJYF can effectively improve 5-HT deficiency in the hippocampus of rats by inhibiting IDO expression and regulating the TRP/KYN metabolic pathway,and it has a favorable protective effect on hippocampal neuron injury caused by DD.Therefore,ZGJTJYF is an effective potential therapeutic drug for the prevention and treatment of DD.

Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.

疏肝解郁安神方干预冠心病合并抑郁状态的代谢组学研究

目的:探究疏肝解郁安神方治疗冠心病合并抑郁状态的作用机制。方法:纳入2021年10月-2022年1月于河南中医药大学第一附属医院心内科住院治疗的冠心病合并抑郁状态病人,采用随机数字表法分为治疗组9例(疏肝解郁安神方+西医常规治疗+心理疏导治疗),对照组8例(西医常规治疗+心理疏导治疗),疗程为1周。利用高效液相色谱-质谱联用技术(HPLC-MS)检测两组病人治疗前后的血清代谢物,筛选潜在的差异代谢物,预测与疏肝解郁安神方治疗冠心病合并抑郁状态相关的代谢通路。结果:冠心病合并抑郁状态病人具有相似的代谢谱特征;通过二级质谱分析,最终共得到26个二级差异代谢物。与干预前冠心病合并抑郁状态病人代谢谱相比,疏肝解郁安神方干预后,黄芩苷、漆黄素、N5-L-1-羧乙基-L-鸟氨酸、5-羟色胺、乌头酸盐、半胱氨酸硫酸酯、5-2-羟乙基-4-甲基噻唑7个代谢物在中药干预后表达水平上调;N-[(3a,5b,7a)-3-羟基-24-氧代-7-(亚砜基)胆聚糖-24-基]-甘氨酸、L-赤霉素、十一烷酸、瓜氨酸、壬酸、氧化苯乙烯6个代谢物在中药干预后表达水平下调;同时对获得的26个二级差异代谢物进行京都基因和基因组百科全书(KEGG)通路富集分析,最终富集到46条代谢通路,富集度最为显著的4条通路分别为环磷酸腺苷信号通路、柠檬酸循环、胆汁分泌、5-羟色胺能突触通路。结论:本研究利用代谢组学技术揭示了疾病和中药复方干预后机体内代谢产物变化,从代谢终端产物层面阐述了疏肝解郁安神方治疗冠心病合并抑郁状态的作用机制,为后续试验的开展和新药的研发提供了一定的参考依据。

名中医康志媛从“肝肾同源于脑”论治多囊卵巢综合征伴抑郁

多囊卵巢综合征伴抑郁是妇科临床常见难题,严重影响女性生殖功能和生活质量,康志媛教授基于“肝肾同源于脑”理论,认为本病与肝肾密切相关。经本于肾,肾主骨生髓通于脑,肾虚不仅冲任胞宫失司经乱,并见髓海空虚则精神失守;水不涵木则肝失调达加重气机不畅,以致形神共病,故发病以肾虚肝郁为主,临证常用经验方补肾疏肝方加减联合五行音乐治疗,药乐结合,共奏补肾疏肝之功,疗效显著。

男性情志问题与肝的相关性研究

目的:通过调查男性人群生活习惯、抑郁情绪、焦虑情绪、自尊水平等,分析男性情志问题与肝的关系,为制定男性情志问题干预策略提供依据。方法:共纳入2023年3—5月符合标准的男238例,通过问卷调查方式采集基本信息、中医肝脏象情绪量表、自尊量表等资料。结果:基本信息显示,调查对象以中青年男性为主,超重及肥胖者占59.7%,喜咸、喜辛辣和喜炙烤者偏多,47.1%有胃肠问题,17.6%有心脏问题,47.9%有睡眠问题,42.9%的男性基本不运动,男性疾病情况显示前列腺炎者14.3%、前列腺增生者4.6%、早泄者10.1%。中医肝脏象情绪量表总分异常者有169例(71.0%),抑郁情绪异常者173例(72.7%),焦虑情绪异常者152例(63.9%),肝经证候异常者134例(56.3%)。在年龄、寒热、喜咸、喜炙烤、睡眠、运动、心脏问题、胃肠问题、前列腺炎、前列腺增生、阳痿等维度,中医肝脏象情绪量表得分差异有统计学意义(P<0.05);抑郁情绪、焦虑情绪与肝经证候因子正相关;自尊水平与中医肝脏象情绪量表总分、抑郁情绪、焦虑情绪、肝经证候因子负相关。结论:男性情志问题与肝的关系密切,调节男性情志应以改善生活习惯、疏肝解郁为主要方法。

朝医补脾泻肾解郁法治疗少阴人中风后郁病气郁证临床观察

目的观察口服朝药十二味宽中汤配合朝医舍岩针法治疗少阴人中风后郁病气郁证的临床效果。方法按照随机数字表法将63例患者以单盲的原则分为治疗组、对照组,对照组31例给予口服盐酸帕罗西汀治疗,治疗组32例给予十二味宽中汤口服结合朝医舍岩针法针刺治疗,疗程1个月。将两组治疗前后汉密尔顿抑郁量表(HAMD)评分进行对比分析。结果治疗后,两组HAMD评分比较,差异有统计学意义(P<0.05)。治疗组总有效率为90.63%(29/32),高于对照组的74.19%(23/31)(P<0.05)。结论朝医补脾泻肾解郁法治疗少阴人中风后郁病气郁证有明显的临床效果,可显著提高治疗总有效率。

基于网络药理学及分子对接探讨四逆散对溃疡性结肠炎与抑郁症“异病同治”的作用机制

目的 基于网络药理学及分子对接探讨四逆散对溃疡性结肠炎与抑郁症“异病同治”的作用机制。方法 利用TCMSP数据库获取四逆散的潜在活性成分及其相关作用靶点;利用GeneCards、CTD、TTD数据库筛选溃疡性结肠炎和抑郁症的疾病相关靶点;对上述预测得到的活性成分作用靶点与疾病相关靶点取交集,获得四逆散治疗溃疡性结肠炎和抑郁症的潜在作用靶点(共有靶点),采用Cytoscape 3.7.2软件构建“中药-活性成分-疾病-共有靶点”网络,分析核心成分;将共有靶点导入STRING数据库,构建共有靶蛋白相互作用(PPI)网络,分析关键靶点;通过DAVID数据库对共有靶点进行GO功能及KEGG通路富集分析;对核心成分与关键靶点进行分子对接验证。结果 共获得四逆散的活性成分136个,四逆散治疗溃疡性结肠炎和抑郁症的潜在作用靶点(共有靶点)220个,涉及657个生物过程、70个细胞组分、147个分子功能以及133条信号通路。筛选得到槲皮素、山柰酚、木犀草素、柚皮素、7-甲氧基-2-甲基异黄酮等核心活性化合物,JUN、MAPK3、STAT3、AKT1、MAPK1等关键靶蛋白,以及TNF、IL-17、Th17细胞分化、HIF-1、Toll样受体等信号通路。5个关键靶点均与槲皮素、山柰酚、木犀草素、柚皮素有较强的结合活性。结论 四逆散可能是通过槲皮素、山柰酚、木犀草素、柚皮素等活性成分,作用于JUN、MAPK3、STAT3、AKT1、MAPK1等关键靶点,通过TNF、IL-17、HIF-1、Toll样受体、Th17细胞分化等信号通路,发挥对溃疡性结肠炎与抑郁症“异病同治”的作用。

从逆、热、郁探讨经方在胃食管反流病中的运用

胃食管反流病与《伤寒杂病论》中部分方证相近,表现出“逆、热、郁”的病机特点。以“逆”为病机的证型有气虚痰逆、阴虚气逆、脾伤饮逆、肝寒浊逆等4型,旋覆代赭汤、麦门冬汤、苓桂术甘汤、吴茱萸汤等方分别治之;以“热”为病机的证型有热郁胸膈、上热下寒等2型,栀子豉汤、黄连汤等方分别治之;以“郁”为病机的证型有邪郁少阳、痰(水)气互阻、痰热互结、阳微阴弦等4型,小柴胡汤、半夏厚朴汤(射干麻黄汤)、小陷胸汤、枳实薤白桂枝汤等方分别治之。应用仲景学说的相关思想可以指导胃食管反流病的治疗。

基于数据挖掘和网络药理学探讨治疗抑郁症的中药复方专利用药规律及机制

目的基于数据挖掘、网络药理学方法,分析探讨治疗抑郁症的中药复方专利用药规律以及核心药物的分子作用机制。方法通过中国专利公布公告网检索获得治疗抑郁症的中药复方,提取中药名称、药味、药性、归经等信息,借助Microsoft Excel 2016、SPSS Modeler 18.0、Cytoscape 3.9.1、中医传承计算平台V3.5软件,对中药进行用药频次、性味归经、关联规则分析,并筛选出核心药物。在数据挖掘基础上,借助中药系统药理数据库与分析平台(TCMSP)获取核心药物的活性成分并预测其作用靶点;通过DisGeNET、GeneCards数据库收集抑郁症靶点,并利用EVenn在线平台获得核心药物治疗抑郁症的潜在靶点;通过STRING 11.5数据库分析蛋白-蛋白相互作用(PPI)及关键靶点网络;借助Cytoscape 3.9.1软件构建核心药物-成分-潜在靶点-通路网络;利用R软件包org.Hs.eg.db(version 3.1.0)和ClusterProfiler(version 3.14.3)对潜在靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。结果①本研究共收集303首中药复方、涉及中药663味,其中使用频次≥30次的中药有26味,共出现1469次,占总频次的39.93%。②本研究涉及的663味中药的药性以温、寒、平为主,药味以甘、苦、辛为主,归经以肝、心、脾、肺、肾、胃为主。③关联规则显示,中药复方治疗抑郁症常用药物组合有15组,涉及中药有当归、柴胡、甘草、郁金、白芍、茯苓等。④网络药理学分析结果显示,中药复方核心药物当归、柴胡、甘草、郁金、酸枣仁、白芍、茯苓的主要活性成分可能是植物甾醇、茯苓酸D、胡萝卜苷、芍药吉酮和当药黄素,这些成分可能作用于非受体酪氨酸蛋白激酶(SRC)、V-Rel网状内皮增生病毒癌基因同源物A(RELA)、蛋白激酶B(AKT)1等关键靶点,并通过调控白介素-17(IL^(-1)7)、C型凝集素受体(CLRs)、肿瘤坏死因子(TNF)、磷脂酰肌醇3激酶(PI3K)/AKT等多条信号通路发挥作用。结论治疗抑郁症的中药复方专利主要涉及疏肝药、理气药、补血药,核心药物有当归、柴胡、甘草、郁金、酸枣仁、白芍、茯苓;其作用机制可能主要与免疫系统信号通路以及神经炎症相关。

基于网络药理学和实验验证探究酸枣仁复方治疗抑郁症的作用机制

目的 通过网络药理学技术预测酸枣仁复方(Ziziphi spinosae semen formula, ZSSF)对于抑郁症的关键作用靶点,并通过利血平诱导的抑郁斑马鱼模型验证酸枣仁复方治疗抑郁症的作用机制。方法 通过TCMSP数据库检索酸枣仁复方的药物作用靶点,利用UniProt数据库对靶点名称进行校正。采用GeneCards、OMIM、NCBI数据库检索抑郁症相关靶点,并对3个数据库的靶点结果进行汇总去比重。利用STRING数据库预测了交集靶点的蛋白质-蛋白质相互作用(protein-protein interaction, PPI)信息,利用Metascape数据库构建进行富集研究,并利用微生信对KEGG和GO的富集结果实现了可视化。通过利血平诱导的斑马鱼抑郁模型进行行为学实验和RT-qPCR实验,验证酸枣仁复方对抑郁症的治疗作用。结果 筛选出抑郁症与酸枣仁复方的交集靶点188个,蛋白质-蛋白质相互作用结果显示,酸枣仁复方抗抑郁主要作用于肿瘤坏死因子-α(TNF-α)、血清白细胞介素2(IL-2)、血清白细胞介素6(IL-6)、血清白细胞介素1β(IL-1β)、血清白细胞介素10(IL-10)等靶点,KEGG通路富集分析表明,酸枣仁复方通过TNF信号通路、PI3K-Akt信号通路、cGMP-PKG信号通路等多种信号通路发挥其治疗抑郁症的作用。动物实验结果显示,与利血平组相比,酸枣仁复方高、中、低剂量组斑马鱼在声光刺激下的运动距离显著延长(P<0.05),运动速度显著增快(P<0.01)。RT-qPCR结果显示,与利血平组相比,酸枣仁复方高、中、低剂量给药组斑马鱼脑组织中TNF-α、IL-2、IL-6、IL-1β、IL-10 mRNA表达水平上调(P<0.001)。结论 酸枣仁复方通过多成分、多靶点发挥抗抑郁作用,且其抗抑郁作用可能与抑制炎症因子的表达有关。

基于网络药理学和动物实验探究逍遥丸治疗骨质疏松症作用机制

目的:基于网络药理学并通过动物实验研究逍遥丸对去卵巢骨质疏松症中小鼠骨结构形态的治疗作用,以及对AGES/RAGE信号转导途径的改变和分子机制。方法:通过TCMSP等数据库搜索逍遥丸药物成分及其成分相关靶点;以“osteoporosis”为关键词,在GeneCards等数据库搜索骨质疏松症相关的靶点;制作韦恩图,获取交集靶点;最后通过DAVID数据库,对药物-疾病交集靶点进行GO与KEGG富集分析并将富集结果可视化。其次,建立小鼠骨质疏松模型,通过CT扫描,HE染色以及免疫组化等检测逍遥丸对成骨分化的影响,并验证网络药理学信号通路预测结果。结果:逍遥丸治疗骨质疏松症的核心活性成分有8种,分别为柴胡、当归、白芍、炒白术、茯苓、炙甘草、薄荷、生姜,合并去重后共得到225个靶点基因。其关键靶点主要参与调控AGEs/RAGE信号通路、IL-17信号通路、TNF信号通路等。在小鼠骨质疏松模型中,逍遥丸能有效提高ALP、COL-1成骨转录因子表达(P<0.05),同时下调AGEs/RAGE信号通路关键蛋白rage、IL-6的表达(P<0.05)。结论:逍遥丸有效改善去卵巢骨质疏松症小鼠骨形态学结构,具有抗去卵巢骨质疏松作用,其机制可能与抑制AGES/RAGE信号通路,提高成骨标志基因ALP、COL-1有关。

中医药对慢性疼痛-抑郁共病的作用机制研究进展

慢性疼痛是指持续或反复发作时间超过3个月的疼痛,与抑郁、焦虑等情绪具有高共病率。慢性疼痛-抑郁共病的发病机制错综复杂,给临床诊疗带来极大困扰。本文综述了近年中药单体和复方以及针刺疗法对慢性疼痛-抑郁共病作用机制的研究进展,发现中药单体(黄酮类、酚类、萜类、香豆素类、生物碱类化合物)、中药复方(乌头汤、柴胡桂枝汤等)及针刺疗法(针刺“百会”“印堂”“合谷”“太冲”等穴位)可以通过调节中枢神经系统中神经递质、脑源性神经营养因子、炎症因子的水平以及神经胶质细胞的活性,有效改善慢性疼痛-抑郁共病。

益肾调气法治疗肾虚肝郁型抑郁障碍远期复发率的多中心前瞻性队列研究

目的:评价益肾调气法对肾虚肝郁型抑郁障碍2年复发率的影响。方法:选取2017年1月至2018年4月在全国13个分中心招募肾虚肝郁型抑郁障碍患者,按照接受的治疗方案自然形成中医组、中西医组和西医组,比较3组的复发率。并根据干预的时间,将中医组和中西医组分为低、中、高3个暴露水平,比较不同水平的复发率,评价益肾调气法降低肾虚肝郁型抑郁障碍的远期复发率的效果。结果:共纳入肾虚肝郁型抑郁障碍1314例,其中中医组385例,西医组453例,中西医组476例。中医组、西医组、中西医组的两年复发率分别是23.61%,34.97%、18.14%。中医组比西医组使复发风险降低29.2%(P<0.05),中西医组比西医组使复发风险降低45.5%(P<0.001)。中医组以低中药水平暴露时间(TCM-ET)为参照,高TCM-ET较于低TCM-ET复发风险降低81.4%(P<0.01);中西医组以低TCM-ET为参照,中TCM-ET比低TCM-ET复发风险降低46.9%(P<0.05),高TCM-ET比低TCM-ET复发风险降低65.3%(P<0.01)。结论:益肾调气法治疗肾虚肝郁型抑郁障碍能够降低远期复发率,且中医药干预的暴露水平与复发率之间具有密切的关系,较长的暴露水平显著降低了患者的复发率。

基于HDAC5/MEF2C通路探讨柴金解郁安神方调节失眠并发抑郁大鼠海马神经元突触可塑性的机制

目的基于组蛋白去乙酰酶5(histone deacetylase 5,HDAC5)/肌细胞增强因子2C(myocyte enhancer factor 2C,MEF2C)通路,探讨柴金解郁安神方调节失眠并发抑郁模型大鼠抑郁样行为及海马神经元突触可塑性的机制。方法通过对氯苯丙氨酸(PCPA)注射联合慢性温和不可预知应激(chronic unpredictable mild stress,CUMS)建立失眠并发抑郁大鼠模型,实验分为空白组、模型组、柴金解郁安神方高、中、低剂量组、阳性药组。通过糖水偏好实验、旷场实验和水迷宫实验评估大鼠的抑郁情况;酶联免疫吸附检测(enzyme linked immunosorbent assay,ELISA)血清中5-羟色胺(5-hydroxytryptamine,5-HT)、多巴胺(dopamine,DA)的水平;HE染色和Nissl染色观察海马神经元病理损伤;高尔基染色(golgi staining)观察海马神经元树突棘损伤情况;免疫印迹法(Western blot)、免疫组化和免疫荧光法检测大鼠海马HDAC5、MEF2C、突触后致密物(postsynaptic density-95,PSD-95)和突触素(synaptophysin 1,SYN1)的表达情况。结果与模型组相比,柴金解郁安神方可以提高模型大鼠的糖水偏好率,减少旷场实验中的不动时间,增加总活动路程,缩短定位航行实验的逃避潜伏期,延长空间探索实验中平台所在象限的停留时间;此外,柴金解郁安神方还能改善海马神经元及树突棘的损伤,增加海马神经元的树突分支长度和树突棘密度;恢复失眠并发抑郁模型大鼠血清中5-HT、DA的水平;下调HDAC5蛋白,上调MEF2C、PSD-95、SYN1蛋白的表达。结论柴金解郁安神方可能通过降低HDAC5蛋白的表达,从而解除对转录因子MEF2C的抑制,促进PSD-95、SNY1蛋白的表达,发挥对海马神经元及突触的保护作用,从而缓解模型大鼠抑郁样行为。

蠲郁安神方治疗肝郁气滞型失眠伴抑郁障碍

目的 观察蠲郁安神方治疗肝郁气滞型失眠伴抑郁障碍的临床疗效。方法 收集肝郁气滞型失眠伴抑郁障碍的患者60例,随机分为观察组和对照组,各30例。对照组单纯口服西药右佐匹克隆治疗,观察组采用蠲郁安神方加减进行治疗,2组均治疗15 d为1个疗程,共治疗2个疗程。比较2组治疗前后匹兹堡睡眠指数量表(PSQI)评价睡眠情况,采用汉密顿抑郁量表(HAMD)评价抑郁状况,使用中医证候积分表评价临床症状。结果 治疗后,观察组肝郁气滞型失眠伴抑郁障碍患者临床总有效率(90.0%,27/30)高于对照组(63.3%,19/30),观察组PSQI总评分、HAMD总评分和中医证候积分均显著低于对照组(P <0.05)。结论 蠲郁安神方治疗肝郁气滞型失眠伴抑郁障碍具有较好的临床疗效,值得临床推广。

温振运气方对嗅球摘除大鼠认知功能及海马区神经递质的影响

目的研究温振运气方对嗅球摘除(OBX)大鼠认知功能及海马区神经递质的影响。方法50只雄性Wistar大鼠分为空白组、假手术组、OBX模型组、OBX中药组、OBX西药组,每组10只。OBX模型组、OBX中药组、OBX西药组大鼠采用嗅球摘除手术建立OBX模型,假手术组不损伤嗅球,其余处理同OBX模型组。造模结束后,OBX中药组予温振运气方5.94 g·kg^(-1)·d^(-1)灌胃,OBX西药组予盐酸多奈哌齐0.45 mg·kg^(-1)·d^(-1)灌胃,OBX模型组、假手术组及空白组予等量的质量分数为0.9%的氯化钠溶液灌胃;各组均连续治疗4周。末次治疗后第1天,各组大鼠进行Morris水迷宫实验、跳台实验、旷场实验检测大鼠认知功能,结束后取各组大鼠海马组织经酶联免疫吸附测定(ELISA)法检测多巴胺(DA)、乙酰胆碱转移酶(ChAT)及γ-氨基丁酸(GABA)含量。结果Morris水迷宫实验中,随着训练天数的逐渐增加,除OBX模型组外,其余各组大鼠逃避潜伏期时间呈缩短趋势。第4~6天,OBX中药组、OBX西药组逃避潜伏期显著短于OBX模型组(P<0.05);第6天,OBX中药组逃避潜伏期长于OBX西药组(P<0.05)。OBX中药组、OBX西药组穿越平台次数、目标象限停留时间均高于OBX模型组(P<0.05);且OBX西药组目标象限停留时间高于OBX中药组(P<0.05)。跳台实验中,OBX中药组、OBX西药组跳下平台错误次数均低于OBX模型组,且仅有OBX西药组跳台潜伏期高于OBX模型组(P<0.05)。旷场实验中,OBX中药组、OBX西药组中央格停留时间均低于OBX模型组(P<0.05);OBX中药组水平运动次数、垂直运动时间与垂直运动次数均高于OBX模型组(P<0.05);OBX西药组垂直运动时间高于OBX模型组(P<0.05)。ELISA法检测结果显示,与OBX模型组比较,OBX中药组、OBX西药组海马区DA、GABA、ChAT浓度升高(P<0.05)。结论温振运气方可通过改变OBX大鼠脑海马区GABA、ChAT、DA浓度达到改善认知功能的目的。

抑郁症态靶辨治策略初探

“态靶辨治”是由仝小林院士首创的中医临床辨治方法,融合了现代科学对于疾病的认识,将中药药理研究成果应用于疾病的中医辨证分型与治疗方药之中,进一步细化了分期分证与临床用药,中西医结合,提高了对疾病辨证用药的精准化与标准化。依据态靶辨治理论体系,本文将抑郁症的总态概括为“郁”,与不同病程兼夹的“瘀”“湿”“痰”“火”“虚”分态。总结确定其调态靶方,和改善症状、调节下丘脑-垂体-肾上腺轴(HPA)与5-羟色胺(5-HT)系统等生物学靶标的靶药,推进抑郁症的“辨证微观化”与“精准用药”。