The Efficacy and Safety of Modified Xiaoyao San for Perimenopausal Syndrome (PMS): A Systematic Review and Meta-Analysis

Objectives: To assess the efficacy and safety of modified Xiaoyao San (XYS) for treating Perimenopausal syndrome (PMS). Methods: Literature searches were carried out on PubMed, Cochrane Library, CNKI Database, Chinese Biomedical Literature Database, Wan Fang Database, and VIP Database up to December 2018. Hand search for further references was conducted. Study selection, data extraction, quality assessment, and data analyses were performed as request of the Cochrane standards. Results: Nine publications in total were suitable for inclusion. There was evidence that modified XYS was tested to be more effective in improving overall symptoms compared with HRT (odds ratio 3.50, 95% CI 2.56 to 4.78). Whereas HRT was more sensitive and direct in decreasing FSH (WMD 6.69, 95% CI 5.60 to 9.52) and LH (WMD 7.00, 95% CI, 5.75 to 8.25) in comparison with XYS group. It was also strongly supported that XYS had less adverse effect than HRT (odds ratio 0.07, 95% CI 0.05 to 0.10). Conclusion: Modified XYS might be more effective and safer in treatment of perimenopausal syndrome. However, due to poor methodological quality in the majority of included studies, the potential benefit and safety about XYS need to be confirmed in rigorously designed, multi-centre, and large-scale trials.

Novel insights into the effect of Xiaoyao san on corticosterone-induced hepatic steatosis:inhibition of glucocorticoid receptor/perilipin-2 signaling pathway

Objective:Xiaoyao san(XYS)is a classic traditional Chinese medicinal formula.It has been clinically administered to regulate liver function.However,its mechanisms in glucocorticoid-induced hepatic steatosis are unknown.This study aimed to investigate whether XYS protects against corticosterone(CORT)-induced hepatic steatosis,and to explore its mechanism.Methods:High-fat diet mice induced with hepatic steatosis by 2mg/kg CORT were administered 2.56 g/kg or 5.12 g/kg XYS daily for 7 weeks.The effects of XYS on hepatic steatosis in mice were evaluated by H&E and Oil Red O staining and by measuring their plasma lipids(triglyceride,total cholesterol,and free fatty acids).The mechanism of XYS against hepatic steatosis was investigated by network pharmacology,immunohistochemistry,western blotting,and gain-of-function/loss-offunction experiments.Results:XYS alleviated CORT-induced steatosis,decreased plasma lipids,and inhibited glucocorticoid receptor(GR)activation in the liver.Network pharmacology data indicated that XYS may have mitigated hepatic steatosis via GR which mediated adipose differentiation-related protein(ADFP).Gain-of-function/loss-of-function experiments in vitro confirmed that GR positively regulated ADFP expression.Conclusions:XYS ameliorated CORT-induced hepatic steatosis by downregulating the GR/ADFP axis and inhibiting lipid metabolism.Our studies implicate that XYS is promising as a therapy for CORT-induced hepatic steatosis,and lay the foundation for designing novel prophylactic and therapeutic strategies on CORT-induced hepatic steatosis.

Effects of Danzhi Xiaoyao pill combined with metformin on related factors in patients with polycystic ovary syndrome

Objective:To study the clinical efficacy and effects of danzhi xiaoyao pill combined with metformin on related factors in patients with polycystic ovary syndrome (PCOS).Methods:A total of 80 patients with PCOS in our hospital from January 2014 to December 2017 were enrolled in this study. The subjects were divided into the control group (n=40) and the experimental group (n=40) randomly. The control group were treated with metformin, the experimental group were treated with danzhi xiaoyao pill combined with metformin, and the two groups were treated for 3 menstrual cycles. The serum CRP, IGF-1, TNF-α, FSH, LH, E2, T, FINS, FPG, VF, LEP, APN and HOMA-IR of the two groups before and after treatment were compared.Results: There were no significantly differences of the serum CRP, IGF-1, TNF-α, FSH, LH, E2, T, FINS, FPG, VF, LEP, APN and HOMA-IR of the two groups before treatment. After treatment, the serum CRP, IGF-1, TNF-α, LH, E2, T, FINS, FPG, VF, LEP and HOMA-IR of the two groups were significantly lower than before treatment, the serum APN of the two groups were significantly higher than before treatment, and that of the experimental group after treatment were significantly better than the control group. Conclusion: Danzhi xiaoyao pill combined with metformin on patients with PCOS has a good efficacy. It can reduce the inflammatory cytokines and sex hormones, and improve the insulin resistance and sugar, lipid metabolic disorders. Therefore, it is worthy of clinical application.

基于肝脏蛋白质组学探讨加味丹栀逍遥散的抗抑郁作用及机制

[目的]探讨加味丹栀逍遥散对慢性不可预知性温和应激(CUMS)抑郁小鼠模型的干预作用及可能机制.[方法]C57BL/6N小鼠分为正常组、模型组、加味丹栀逍遥散组和氟西汀组.采用CUMS复制抑郁模型,模型成功后灌胃给药4周.末次给药后进行行为学测试,采用串联质谱标签法(TMT)蛋白质组学分析小鼠肝脏差异蛋白的表达谱,通过Kyoto encyclopedia of genes and genomes(KEGG)通路富集加味丹栀逍遥散抗抑郁的相关通路和蛋白;血液生化检测总胆固醇及总胆汁酸含量.[结果]与正常组相比,模型组小鼠糖水偏好率下降,自主活动次数减少,加味丹栀逍遥散给药后上调小鼠糖水偏好率及自主活动次数.蛋白组学结果显示模型组与加味丹栀逍遥散给药组之间肝脏差异表达蛋白20个,其中上调11个,下调9个.KEGG通路富集分析发现差异表达蛋白主要参与了胆固醇代谢、初级胆汁酸的合成等.生化检测发现,与正常组相比,模型组总胆固醇含量下降而胆汁酸含量升高,加味丹栀逍遥散给药能显著增加总胆固醇含量而减少总胆汁酸含量.[结论]加味丹栀逍遥散具有良好的抗抑郁效应,其机制可能与调节肝脏胆固醇异常代谢、降低血液总胆汁酸有关.

Effect of Xiaoyao San on the brain-gut axis in rats after chronic immobilization stress

Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days,during which they were administered Xiaoyao San decoction [3.854 g/(kg· d)] or vehicle by gavage,and their body weight gain,food intake and water intake were monitored.The rats were subsequently subjected to the open field test (OFT) and D-XyloSe absorption test,and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA),radioimmune analysis,or real-time fluorescence quantitative polymerase chain reaction.Gastric mucosal morphology was also assessed.Results:The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS,abnormalities signified by decreases in food intake,reductions in digestive absorption,decreases in body weight,decreases in the total distances traveled and increases in the time in the central zone during the OFT,gastric mucosal lesion development and decreases in gastrointestinal hormone secretion.These changes were reversed after treatment with Xiaoyao San,which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides.Specifically,the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5,which are secreted by the hypothalamus and promote digestive function,were increased in the Xiaoyao San-treated group compared with the model group.Furthermore,the levels of pro-opiomelanocortin (POMC) and its receptor,melanocortin-4 receptor (MC4R),which are secreted by the hypothalamus and inhibit digestive function,were significantly decreased in the treatment group compared with the model group.However,the levels of ghrelin (GHRL),gastrin (GAS) and motilin (MTL),which are secreted by the stomach,were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P <.05 vs.the model group).Conclusion:Xiaoyao San attenuates CIS-induced gastrointestinal dysregulation by regulating the peptides secreted by both the hypothalamus and the gastrointestinal tract (GIT),suggesting that its effects are associated with the brain-gut axis.

Use of Danzhi Xiaoyao Powder in the Treatment of Diseases by Chief Physician Wang Defen: Case Examples

Danzhi Xiaoyao powder was first introduced by Xue Ji,a Ming Dynasty physician,in the“Summary of Internal Medicine.”It is primarily used for treating the syndrome of liver depression transforming into heat and is widely used in the treatment of dermatology,internal medicine,gynecology,and other multi-system diseases.This medical prescription is aptly dispensed,its detoxification effect is strong,and it is a representative medical prescription for soothing the liver,strengthening the spleen and stomach,as well as eliminating heat stagnation.Chief Physician Wang Defen inherited the academic experience of the fifth batch of nationally known Chinese medicine experts,under the guidance of Professor Ji Haiwang,a notable Chinese medicine practitioner in Shaanxi Province and Professor Shi Bingyin,a renowned endocrinologist.Through follow-up studies,the various methods and empirical prescriptions of Danzhi Xiaoyao powder applied by Chief Physician Wang Defen in the treatment of common clinical diseases are summarized.They have been proven to have conclusive efficacy,thus providing guidance and reference for the dialectical treatment using traditional Chinese medicine.

丹栀逍遥散加减方对精神分裂症患者高催乳素血症的影响研究

目的观察丹栀逍遥散加减方对精神分裂症患者高催乳素水平的影响。方法将118例精神分裂症并发有高催乳血症患者按照随机数字表法分为2组,2组均常规给予抗精神分裂症药物治疗,治疗组56例予丹栀逍遥散加减方治疗,对照组62例予安慰剂治疗。2组均治疗12周后。比较2组治疗前及治疗4、12周血清催乳素、精神症状[采用阳性和阴性症状量表(PANSS)评分进行评价]及生活质量[采用精神分裂症患者生活质量量表(SQLS)进行评价,包括心理社会、动机/精力、症状/副反应3个方面]变化情况,统计分析治疗组治疗12周后血清催乳素水平与PANSS评分、SQLS评分之间的相关性。结果与本组治疗前比较,治疗组治疗4、12周血清催乳素水平均降低(P<0.05),且治疗组治疗4、12周血清催乳素水平均低于对照组同期(P<0.05),但对照组治疗4、12周血清催乳素水平与治疗前比较差异均无统计学意义(P>0.05)。2组治疗4、12周PANSS评分与本组治疗前比较及组间比较差异均无统计学意义(P>0.05)。与本组治疗前比较,治疗组治疗4、12周SQLS心理社会、动机/精力、症状/副反应评分及总分均降低(P<0.05),且治疗组治疗4、12周SQLS心理社会、动机/精力、症状/副反应评分及总分均低于对照组同期(P<0.05),但对照组治疗4、12周SQLS心理社会、动机/精力、症状/副反应评分及总分与治疗前比较差异均无统计学意义(P>0.05)。经Pearson相关性分析显示,治疗组治疗12周血清催乳素水平与SQSL症状/副反应评分及总分存在正相关性(r=0.259,P=0.005;r=0.263,P=0.004)。结论丹栀逍遥散加减方治疗精神分裂症患者高催乳素血症临床疗效确切,可有效降低患者血清催乳素水平,提高患者生活质量,是一种颇具治疗效应的临床辅助治疗手段。

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。

经方丹栀逍遥丸对代谢相关脂肪性肝病小鼠巨噬细胞增殖活性及防炎癌作用的影响及机制研究

目的 评价经方丹栀逍遥丸(JF-DZXYW)含药血清对代谢相关脂肪性肝病小鼠巨噬细胞增殖活性及防炎癌转化的调控,并阐述其诱导免疫系统发挥抗炎、抗肿瘤作用。方法 40只体质量18~22 g雄性昆明种小鼠,随机分为对照组(生理盐水组)、JF-DZXYW低剂量组(125μg/mL)、JF-DZXYW中剂量组(250μg/mL)和JF-DZXYW高剂量组(500μg/mL),灌胃0.4 mL/次,1次/d,共3 d。第4天灌胃后行小鼠腹主动脉取血,分离血清。采用CCK-8法检测各剂量组含药血清对小鼠巨噬细胞株Raw 264.7细胞增殖的影响,并筛选出最佳给药浓度。酶联免疫吸附测定(enzyme linked immunosorbent assay, ELISA)法检测细胞因子:肿瘤坏死因子-α(tumor necrosis factor, TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、干扰素-β(interferon-β,IFN-β)、白细胞介素-12(interleukin-12p40,IL-12p40)、白细胞介素-10(interleukin-10,IL-10)含量。运用MTT法分析HepG2肝癌细胞被巨噬细胞杀伤的效果。结果 小鼠巨噬细胞培养12 h后,JF-DZXYW各剂量组含药血清处理组巨噬细胞增殖速度与对照组相比无显著升高(P>0.05);细胞培养24 h后,JF-DZXYW各剂量组含药血清处理组巨噬细胞增殖速度与对照组相比显著升高(P<0.01)。JF-DZXYW中、高剂量组含药血清可显著提升细胞因子TNF-α、IL-1β含量,与对照组相比差异有统计学意义(P<0.01);JF-DZXYW低、中、高剂量组含药血清可显著提升细胞因子IL-6含量,与对照组相比差异有统计学意义(P<0.01);JF-DZXYW中剂量组含药血清可显著提升细胞因子IL-12p40、IFN-β含量,与对照组相比差异有统计学意义(P<0.05);JF-DZXYW高剂量组含药血清可显著提升细胞因子IL-12p40、IFN-β含量,与对照组相比差异有统计学意义(P<0.01);JF-DZXYW高剂量组含药血清可显著提升细胞因子IL-10含量,与对照组相比差异有统计学意义(P<0.01);JF-DZXYW低、中剂量组含药血清可显著提升细胞因子IL-10含量,与对照组相比差异有统计学意义(P<0.05)。JF-DZXYW各剂量组含药血清细胞杀瘤率显著升高,与对照组相比差异有统计学意义(P<0.01)。结论 JF-DZXYW可以通过上调巨噬细胞增殖活性、诱导免疫系统发挥抗炎、抗肿瘤作用。

经方丹栀逍遥丸对代谢相关脂肪性肝病小鼠巨噬细胞抗慢炎状态的调节作用

目的 评价经方丹栀逍遥丸(JF-DZXYW)对代谢相关脂肪性肝病小鼠巨噬细胞抗慢性炎症的调控作用,对巨噬细胞吞噬能力、巨噬细胞表面标志物MHC-Ⅱ、CD86、CD80、TLR4表达及巨噬细胞内活性氧表达(ROS)的影响,并阐述其诱导免疫系统发挥抗炎症作用。方法 40只体质量18~22 g雄性昆明种小鼠,随机分为对照组(生理盐水组)、JF-DZXYW低剂量组(125μg/mL)、JF-DZXYW中剂量组(250μg/mL)和JF-DZXYW高剂量组(500μg/mL),灌胃0.4 mL/t/d,共15 d。第16天小鼠行腹腔注射0.2 mL 10%蛋白胨,3 d后小鼠腹腔注射新配制的5%鸡红细胞各0.5 mL,提取小鼠腹腔巨噬细胞进行巨噬细胞吞噬功能检测、细胞表面标志物流式细胞分析及ROS表达检测。结果 3个剂量组的JF-DZXYW汤剂吞噬百分率及吞噬指数均显著高于对照组(P<0.01)。JF-DZXYW低、中、高剂量组小鼠腹腔巨噬细胞表面标志物MHC-Ⅱ、CD86、CD80表达明显高于对照组(P<0.01),JF-DZXYW中、高剂量组小鼠腹腔巨噬细胞表面标志物TLR4表达均明显高于对照组(P<0.01)。JF-DZXYW低剂量组小鼠腹腔巨噬细胞内ROS表达明显高于对照组(P<0.05),JF-DZXYW中、高剂量组小鼠腹腔巨噬细胞内ROS表达均明显高于对照组(P<0.01)。结论 JF-DZXYW可以通过上调巨噬细胞功能、促巨噬细胞表面标志物MHC-Ⅱ、CD86、CD80、TLR4及巨噬细胞内活性氧表达提升机体免疫功能从而抑制慢性炎症状态。

逍遥散联合水飞蓟素胶囊治疗肝郁脾虚证非酒精性脂肪性肝病临床研究

目的:逍遥散联合水飞蓟素胶囊治疗肝郁脾虚证非酒精性脂肪性肝病(NAFLD)的疗效。方法:选取90例肝郁脾虚证NAFLD患者,按随机数字表法分为对照组及治疗组各45例。2组行非药物措施,对照组予以水飞蓟素胶囊口服,治疗组在对照组基础上加逍遥散治疗。2组均连续治疗12周。比较2组临床疗效,比较2组治疗前后肝功能指标[谷草转氨酶(AST)、丙氨酸转氨酶(ALT)、谷氨酰转肽酶(GGT)]值、血脂指标[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]值、血清TLR4/NF-κB信号通路相关蛋白水平[血清TOLL样受体4(TLR4)、髓样分化因子88(MyD88)、核转录因子-κB(NF-κB)]、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的变化。结果:治疗12周后,治疗组临床疗效总有效率为91.11%,对照组为73.33%,2组比较,差异有统计学意义(P<0.05)。治疗12周后,2组AST、ALT、GGT指标值均较治疗前下降(P<0.05),治疗组上述3项指标值均低于对照组(P<0.05)。治疗12周后,2组TC、TG、LDL-C水平均较治疗前下降(P<0.05),HDL-C水平均较治疗前上升(P<0.05);治疗组TC、TG、LDL-C水平均低于对照组(P<0.05),HDL-C水平高于对照组(P<0.05)。治疗12周后,2组血清TLR4、MyD88、NF-κB、IL-6、TNF-α水平均较治疗前下降(P<0.05),治疗组上述5项水平均低于对照组(P<0.05)。结论:逍遥散联合水飞蓟素胶囊对肝郁脾虚证NAFLD的疗效确切,可有效改善肝功能及血脂状况,调节血清TLR4-NF-κB信号通路,抑制炎症反应。

基于网络药理学研究丹栀逍遥散治疗便秘的作用机制

目的基于网络药理学研究丹栀逍遥散治疗便秘的作用机制。方法利用TCMSP、BATMAN-TCM、Uniprot、GeneCards等数据库检索筛选丹栀逍遥散关键成分及相关靶点、疾病靶点和相关通路。通过STRING数据库和Cytoscape软件绘制PPI网络图,寻找核心基因。利用Metascape和BioGPS数据库通过微生信平台进行基因富集分析。利用SwissDock平台进行分子对接分析。结果丹栀逍遥散药物靶点746个,便秘靶点1620个。关键靶点为VEGFA、CASP3、TNF、JUN,关键成分为槲皮素、β-谷甾醇、山奈酚、豆甾醇。关键靶点主要作用于淋巴细胞、平滑肌、结肠、结直肠腺癌、小肠,主要富集于炎性肠病、NF-κB信号通路等。分子对接结果显示活性成分与靶点蛋白结合稳定。结论丹栀逍遥散治疗便秘的作用机制,可能是通过其4个关键成分作用于4个关键靶点,调节多通路,起到抑制炎症、保护肠黏膜屏障、调节肠道菌群等作用。

朱氏头皮针联合丹栀逍遥散治疗肝郁化火型耳鸣的临床观察

【目的】观察朱氏头皮针联合丹栀逍遥散治疗肝郁化火型耳鸣的临床疗效。【方法】将70例肝郁化火型耳鸣患者随机分为治疗组和对照组,每组各35例。治疗组给予朱氏头皮针联合丹栀逍遥散治疗,对照组给予银杏叶片与甲钴胺片治疗,疗程为3周。治疗3周后,评价2组临床疗效,并于治疗结束后3、6个月进行电话随访,评价临床疗效。观察2组患者治疗前后耳鸣评价量表(TEQ)评分的变化情况,以及焦虑自评量表(SAS)评分的情况。比较2组患者治疗前后耳鸣残疾评估量表(THI)评分的变化情况。并评价2组的安全性及不良反应的发生情况。【结果】(1)治疗后,治疗组总有效率88.57%(31/35),对照组为62.86%(22/35),治疗组疗效优于对照组,差异有统计学意义(P<0.05)。(2)治疗后,2组患者TEQ、SAS、THI评分均明显改善(P<0.01),且治疗组在改善TEQ、SAS、THI评分方面明显优于对照组,差异均有统计学意义(P<0.05)。(3)治疗结束后3个月随访,治疗组的总有效率为85.71%(30/35),对照组为60.00%(21/35)。治疗结束后6个月随访,治疗组的总有效率为82.86%(29/35),对照组为54.29%(19/35)。治疗结束后3、6个月随访,治疗组疗效均优于对照组,差异均有统计学意义(P<0.05)。(4)2组患者均未见明显不良反应。2组患者的不良反应发生率比较,差异无统计学意义(P>0.05)。【结论】朱氏头皮针联合丹栀逍遥散治疗肝郁化火型耳鸣,可明显改善患者的耳鸣症状,安全性高,无不良反应,疗效显著。

逍遥散合大黄[庶虫]虫丸治疗原发性肝癌经肝动脉化疗栓塞术后气滞血瘀型疗效研究

目的:研究逍遥散合大黄[庶虫]虫丸对经肝动脉化疗栓塞(TACE)术后的原发性肝癌(PLC)患者气滞血瘀型的治疗效果。方法:将80例肝癌气滞血瘀型患者采用随机数字表法分为观察组和对照组各40例。对照组肝癌患者TACE术后予对症治疗,观察组肝癌患者在对症治疗的基础上联合逍遥散合大黄[庶虫]虫丸进行治疗。经治疗1个月后复查肝功能、凝血功能、肿瘤指标及上腹部影像学检查的变化情况。结果:观察组血清甲胎蛋白(AFP)、糖类抗原199(CA199)、糖类抗原125(CA125)等肿瘤指标,谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、总蛋白(TP)、白蛋白(ALB)等肝功能指标,凝血酶原时间(PT)、凝血酶原活动度(PTA)、国际标准化比值(INR)、纤维蛋白原(FIB)等凝血功能指标低于对照组,差异具有统计学意义(P<0.05),观察组总有效率75.00%,获益率90.00%,对照组总有效率32.50%,获益率57.50%,观察组总有效率高于对照组(P<0.05)。结论:肝癌气滞血瘀型患者在经过TACE术后,在对症治疗的基础上加用中药内服方逍遥散合大黄[庶虫]虫丸具有更好的疗效,逍遥散合大黄[庶虫]虫丸可以加强对肝功能的保护,有效地改善凝血功能,降低肝癌的转移程度。

丹栀逍遥散合甘麦大枣汤联合疏肝调神针法对偏头痛临床疗效及血清指标变化的影响

目的 分析丹栀逍遥散合甘麦大枣汤联合疏肝调神针法对偏头痛临床疗效及对血清肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)和降钙素基因相关肽(Calcitonin gene related peptide, CGRP)水平的影响。方法 选择齐齐哈尔市中医医院2020年3月—2022年3月收治的126例偏头痛患者,使用随机数字表法分别纳入联合组(n=63)、对照组(n=63)。两组均给予盐酸氟桂利嗪片口服,并给予疏肝调神针法针灸治疗,联合组加用丹栀逍遥散合甘麦大枣汤,持续1个月。对比两组治疗前后头痛症状、生活质量变化,并比较两组治疗前后脑血流动力学、血清指标变化,分析两组临床疗效。结果 头痛症状方面,两组治疗1个月后头痛发作频率、每月无头痛天数、发作时疼痛视觉模拟评分(Visual Analog Scale, VAS)、单次头痛持续时间均较治疗前下降;联合组治疗1个月后头痛发作频率、每月无头痛天数、发作时VAS评分、单次头痛持续时间均低于对照组,差异有统计学意义(P<0.05)。生活质量方面,两组治疗1个月后偏头痛生活品质问卷(Migraine-SpecificQualityLifeQuestionnaire, MSQ)量表各维度评分及总分均较治疗前下降;联合组治疗1个月后MSQ量表各维度评分及总分均低于对照组,差异有统计学意义(P<0.05)。脑血流动力学方面,两组治疗1个月后双侧大脑中动脉(middle cerebral artery, MCA)、基底动脉(Basilar artery, BA)、大脑后动脉(Posterior cerebral artery, PCA)、大脑前动脉(Anterior cerebral artery, ACA)血流速度均较治疗前下降;联合组治疗1个月后MCA、BA、PCA、ACA血流速度均低于对照组,差异有统计学意义(P<0.05)。血清指标方面,两组治疗1个月后血清TNF-α、ICAM-1、CGRP均较治疗前下降;联合组治疗1个月后血清TNF-α、ICAM-1、CGRP均低于对照组,差异有统计学意义(P<0.05)。联合组治疗1个月后总有效率为90.48%,高于对照组的74.60%,差异有统计学意义(P<0.05)。结论 在疏肝调神针法的基础上,将丹栀逍遥散合甘麦大枣汤应用于偏头痛的治疗,不仅有助于改善患者头痛症状、脑血流动力学、生活质量,也能够改善血清TNF-α、ICAM-1、CGRP,从而达到更为理想的临床疗效。

Effects of Xiaoyao San on exercise capacity and liver mitochondrial metabolomics in rat depression model

Objective: This study aimed to investigate the therapeutic effects of Xiaoyao San(XYS), a herbal medicine formula, on exercise capacity and liver mitochondrial metabolomics in a rat model of depression induced by chronic unpredictable mild stress(CUMS).Methods: A total of 24 male SD rats were randomly divided into four groups: control group(C), CUMS control group(M), Venlafaxine positive treatment group(V), and XYS treatment group(X). Depressive behaviour and exercise capacity of rats were assessed by body weight, sugar-water preference test, open field test, pole test, and rotarod test. The liver mitochondria metabolomics were analyzed by using liquid chromatography-mass spectrometry(LC-MS) method. TCMSP database and Gene Cards database were used to screen XYS for potential targets for depression, and GO and KEGG enrichment analyses were performed.Results: Compared with C group, rats in M group showed significantly lower body weight, sugar water preference rate, number of crossing and rearing in the open field test, climbing down time in the pole test,and retention time on the rotarod test(P < 0.01). The above behaviors and exercise capacity indices were significantly modulated in rats in V and X groups compared with M group(P < 0.05, 0.01). Compared with C group, a total of 18 different metabolites were changed in the liver mitochondria of rats in M group.Nine different metabolites and six metabolic pathways were regulated in the liver mitochondria of rats in X group compared with M group. The results of network pharmacology showed that 88 intersecting targets for depression and XYS were obtained, among which 15 key targets such as IL-1β, IL-6, and TNF were predicted to be the main differential targets for the treatment of depression. Additionally, a total of 1 553 GO signaling pathways and 181 KEGG signaling pathways were identified, and the main biological pathways were AGE-RAGE signaling pathway, HIF-1 signaling pathway, and calcium signaling pathway.Conclusion: XYS treatment could improve depressive symptoms, enhance exercise capacity, positively regulate the changes of mitochondrial metabolites and improve energy metabolism in the liver of depressed rats. These findings suggest that XYS exerts antidepressant effects through multi-target and multi-pathway.

加味逍遥散通过外泌体miRNA途径发挥抗肝癌作用

背景:在课题组先前研究中发现加味逍遥散具有明显的抗肝癌作用,但具体作用机制不明。目的:基于高通量测序结合生物信息学,探讨加味逍遥散对二乙基亚硝胺慢性诱导的原发性肝癌模型大鼠血浆外泌体miRNA水平的调节作用。方法:将SD大鼠随机分为空白对照组、肝癌模型组、加味逍遥散组。以二乙基亚硝胺持续给药12周诱导肝癌模型,从第17周开始,加味逍遥散组大鼠给予加味逍遥散灌服,每日1次,直至第20周末停药,空白对照组和肝癌模型组大鼠给予等量生理盐水灌胃,通过检测大鼠肝组织的形态结构、肝癌标志物Glypican-3蛋白和血清甲胎蛋白表达验证抗肝癌效应。使用超速离心法分离提取各组大鼠血浆外泌体,利用高通量测序技术筛选出大鼠血浆外泌体中差异表达的miRNA,生物信息学预测加味逍遥散通过肝癌血浆来源外泌体miRNA发挥抗肝癌作用的潜在生物标志物,并进行功能分析。结果与结论:①加味逍遥散对肝癌模型大鼠肝组织的形态结构有显著改善作用,与肝癌模型组相比,加味逍遥散组肝癌标志物Glypican-3蛋白和血清甲胎蛋白的表达均显著降低;②生物信息学分析显示,加味逍遥散组对肝癌模型组上调的miR-223-3p与基因E2F1、NCOA1存在靶向结合位点,并且与肝癌生存率及预后密切相关。由此可见,加味逍遥散对肝癌有治疗作用,可能是通过肝癌血浆来源外泌体miR-223-3p靶向负调控NCOA1/E2F1进而发挥抗肝癌效应。

基于网络药理学和分子对接技术探讨丹栀逍遥散“异病同治”抑郁伴干眼的作用机制

目的:应用网络药理学方法和分子对接技术探讨丹栀逍遥散治疗抑郁伴干眼的作用机制。方法:首先借助中药系统药理学数据库与分析平台(TCMSP)获取并筛选丹栀逍遥散的成分靶点,结合OMIM数据库、DRUGBANK数据库、TTD数据库和GeneCards数据库获取疾病靶点,得到丹栀逍遥散治疗抑郁症和干眼的靶点,再用Cytoscape 3.7.1软件绘制丹栀逍遥散“单一药物-有效成分-共同靶点”网络图,寻找治疗抑郁伴干眼的关键靶点,然后对两种疾病的共同靶点进行京都基因与基因组百科全书(KEGG)通路富集分析和基因本体论(GO)富集分析,最终将关键活性成分与核心靶点进行分子对接。结果:本研究共收集到丹栀逍遥散“异病同治”抑郁伴干眼有效成分128种,丹栀逍遥散“异病同治”靶点52个。关键的生物学通路涵盖癌症通路、糖尿病并发症中的晚期糖基化终末产物(Advanced Glycation End Product,AGE)-晚期糖基化终末产物受体(Advanced Glycation End Product Receptor,RAGE)信号通路等。丹栀逍遥散治疗抑郁伴干眼的核心靶蛋白为肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素(Interleukin,IL)-6、IL-1B、血管内皮生长因子(Vascular Endothelial Growth Factor,VEGF)A、半胱氨酸蛋白酶3(Caspase 3,CASP3)、信号转导和转录激活因子3(Signal Transducers and Activators of Transcription 3,STAT3)等,关键活性成分涵盖山柰酚、槲皮素、柚皮素、芍药苷、木犀草素、芦荟大黄素等,分子对接的结果显示丹栀逍遥散中的关键活性成分与对应的靶点结合效果良好。结论:丹栀逍遥散可通过控制炎症反应治疗抑郁伴干眼。本研究结果为深入了解丹栀逍遥散治疗抑郁伴干眼的作用机制和探索其新的药理作用提供理论依据,也为中医科学内涵的解读指明新的思路和方向。

丹栀逍遥散在眼科中应用的研究进展

丹栀逍遥散擅治肝郁血虚之证,作为中医眼科常用方剂,深入研究该方对挖掘本方的临床价值有重要意义。对该方从古至今进行梳理,发现其临床应用范围逐渐扩大,且在中医眼科中较为常用。本文综述了丹栀逍遥散的现代临床应用,总结相关药理作用与作用机制,发现丹栀逍遥散可以通过抗炎、调节细胞免疫、神经保护等方式干预干眼、视神经疾病、葡萄膜炎等眼病,具有较好疗效。但中医药治疗疾病常通过多成分、多途径、多靶点发挥作用,丹栀逍遥散作用机制尚待进一步完善,本研究可为今后丹栀逍遥散在眼科中的应用提供参考。

董氏奇穴联合中药治疗混合性焦虑抑郁障碍痰气郁结证的疗效观察

目的:观察针刺董氏奇穴联合内服中药治疗混合性焦虑抑郁障碍(Mixed Anxiety and Depressive Disorder,MADD)痰气郁结证的疗效。方法:选择2020年4月至2021年10月江海区中西医结合医院治疗的MADD患者90例,随机分为对照组、观察A组、观察B组各30例。对照组予口服氟哌噻吨美利曲辛片,观察A组予内服温胆汤合丹栀逍遥散加减,观察B组在观察A组治疗的基础上予针刺董氏奇穴,均治疗12周,治疗后对比三组患者的医院焦虑抑郁量表(Hospital Anxiety and Depression Scale,HADS)评分、中医证候评分、临床疗效及不良反应。结果:治疗前,三组患者的HADS评分、痰气郁结证评分对比,差异无统计学意义(P>0.05);治疗后,三组患者的HADS评分、痰气郁结证评分均较治疗前下降(P<0.05),其中观察A组、观察B组的HADS评分、痰气郁结证评分均明显低于对照组(P<0.05),观察B组的HADS评分、痰气郁结证评分均明显低于观察A组(P<0.05)。观察B组的总有效率(93.33%)高于观察A组(86.67%)、对照组(73.33%)(P<0.05)。治疗期间,对照组不良反应发生率为13.33%,观察A组为6.67%,观察B组为10.00%,差异无统计学意义(P>0.05)。结论:针刺董氏奇穴联合内服中药具有行气开郁、化痰散结、清肝泻火之功效,治疗MADD痰气郁结证安全有效,值得在临床中推广应用。