Pharmacodynamic study and mechanism of action of Linggui Zhugan Decoction in the intervention of Nonalcoholic fatty liver disease

Objective: To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments, and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology. Methods: A rat model of non- alcoholic fatty liver disease was established after 20 weeks of high-fat feeding, and the rats were divided into six groups, normal group, model group, simvastatin group (4 mg/kg), low- dose group of Linggui Zhugan Decoction (2.1 g/kg), medium-dose group of Linggui Zhugan Decoction (4.2 g/kg), and high-dose group of Linggui Zhugan Decoction (8.4 g/kg), and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed, and the microplate reader detected aspartate aminotransferase, alanine aminotransferase, Four levels of blood lipids. Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease. Results: Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats (P<0.05). HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group. Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats (P<0.05). Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets. Conclusion: The results show that Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease, and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.

加味苓桂术甘汤对阳虚水停证慢性心力衰竭患者TGF-β1、TNF-α、NT-proBNP及心室重构的影响

目的探究加味苓桂术甘汤对阳虚水停证慢性心力衰竭患者TGF-β1、TNF-α、NT-proBNP及心室重构的影响。方法将2017年12月至2020年11月六安市中医院收治的98例阳虚水停证慢性心力衰竭患者纳入本研究,随机分为两组,各49例。对照组行西医常规治疗,观察组在此基础上行加味苓桂术甘汤口服治疗,治疗6个月后检测心功能,血清肿瘤坏死因子(tumor necrosis factor,TNF)-α、转化生长因子(transforming growth factor,TGF)-β1、同型半胱氨酸(homocysteine,Hcy)、氨基末端脑钠素原(amminoterminal brain sodium minogen,NT-proBNP)水平并比较临床疗效。结果两组患者治疗后各项指标均较治疗前明显改善(P<0.05)。其中观察组患者治疗后血清TNF-α、TGF-β1、Hcy、NT-proBNP、左室舒张末期内径、左室收缩末期内径和中医证候总积分低于对照组,左室射血分数、6 min步行距离和临床疗效高于对照组(P<0.05)。结论加味苓桂术甘汤治疗阳虚水停证慢性心力衰竭可减轻患者炎症反应,预防心室重构,提高临床疗效。

从“微饮”立论射血分数保留的心力衰竭早期防治思想

射血分数保留的心力衰竭(heart failure with preserved ejection fraction, HFpEF)是目前心血管领域的治疗难点,防治前线前移对于减缓或逆转HFpEF发病进程至关重要。聚焦HFpEF早期的中医防治,是发挥中医治未病优势的关键。通过梳理仲景提出的“微饮”内涵和证治,结合HFpEF早期的发病机制,提出HFpEF早期以微饮内停上焦为主要病机,临证应以苓桂术甘汤为主祛饮通阳,以期阻断饮证进一步发展,截断HFpEF发展进程。从“微饮”立论HFpEF早期防治,可以防微杜渐,具有重要的临床意义。

苓桂术甘汤干预非酒精性脂肪肝病的药效学研究及作用机制探讨

目的:通过体内动物实验探究苓桂术甘汤对非酒精性脂肪肝病的治疗效果,网络药理学及分子对接技术探究苓桂术甘汤干预非酒精性脂肪肝病的作用机制。方法:高脂喂养20周建立非酒精性脂肪肝病大鼠模型,将大鼠分为6组,正常组、模型组、辛伐他汀组(4 mg/kg)、苓桂术甘汤低剂量组(2.1 g/kg)、苓桂术甘汤中剂量组(4.2 g/kg)、苓桂术甘汤高剂量组(8.4 g/kg),观察苓桂术甘汤干预后的HE染色及油红O染色的肝脏形态学变化,酶标仪检测血清中谷草转氨酶、谷丙转氨酶、血脂四项水平。利用网络药理学结合分子对接筛选苓桂术甘汤干预非酒精性脂肪肝病潜在作用机制及靶点。结果:苓桂术甘汤可显著改善模型大鼠的谷草转氨酶、谷丙转氨酶水平(P<0.05);HE染色和油红O染色显示苓桂术甘汤显著降低模型组大鼠的肝脏脂质沉积;苓桂术甘汤可显著降低模型大鼠血脂四项水平(P<0.05);网络药理学筛选出关键靶点10个,关键信号通路5条;分子对接结果表明前20活性成分均对前十靶点有良好结合能力。结论:表明苓桂术甘汤对非酒精性脂肪肝病有调节血脂及改善肝组织病变作用,并初步验证了苓桂术甘汤对脂质代谢相关基因的调控作用。

Identification of Cald1 as a novel regulator of Linggui Zhugan decoction(苓桂术甘汤) for improving insulin resistance in vivo and in vitro

OBJECTIVE:To identify Cald1 as a novel regulator of Linggui Zhugan decoction(苓桂术甘汤)for improving insulin resistance in vivo and in vitro.METHODS:Sprague-Dawley rats were randomly assigned to 3 groups that were received a normal rat chow diet,high-fat diet(HFD),and an HFD plus LGZGD,respectively.The homeostatic model assessment(HOMA)-insulin resistance(IR)index was used to determine IR.Gene microarray methodology was used to identify differentially expressed genes(DEGs)in the three groups of rats.The DEGs associated with IR were confirmed by quantitative real-time polymerase chain reaction.Additionally,Mouse 3 T3-L1 pre-adipocytes were differentiated into mature 3 T3-L1 adipocytes,which were then treated with tumor necrosis factor(TNF)-αto induce cellular IR.Lipid accumulations were identified by Oil Red O staining.Glucose uptake was assessed using the3 H-2-DG test.RESULTS:In this study,we found Cald1 was further screened to validate its biological function in3 T3-L1 adipocytes induced to develop IR.In vitro experiments showed that insulin-stimulated 3 H-2-DG uptake by IR 3 T3-L1 adipocytes was increased after LGZGD intervention,which was associated with a down-regulation of Cald1 expression.CONCLUSION:LGZGD ameliorates HFD-induced IR in rats and TNF-αinduced IR in adipocytes by down-regulating Cald1 expression.

基于UPLC指纹图谱结合化学计量学的经典名方苓桂术甘汤质量评价研究

目的建立指纹图谱与化学计量学相结合的经典名方苓桂术甘汤的质量评价方法。方法使用SHIMADZU Shim-Pack GIST C18色谱柱(100 mm×2.1 mm,2.0μm),流动相为乙腈-0.1%磷酸水溶液,梯度洗脱,柱温30℃,流速0.2 mL/min,检测波长为266 nm(前30 min)、235 nm(后36 min)。使用《中药色谱指纹图谱相似度评价系统》(2012.130723版)建立苓桂术甘汤超高效液相色谱指纹图谱,确定共有峰并进行相似度评价;基于指纹图谱共有峰峰面积测定结果,采用聚类分析、主成分分析和正交偏最小二乘-判别分析(OPLS-DA)对不同批次苓桂术甘汤进行质量评价。结果共确认苓桂术甘汤指纹图谱24个共有峰,使用对照品指认14个共有峰,10批苓桂术甘汤样品相似度均大于0.950。10批苓桂术甘汤可聚为两类,主成分1~4是影响其质量评价的主要因子,OPLS-DA共确定6个差异标志物。结论本研究建立的指纹图谱方法简便可靠,重复性良好,指纹图谱结合化学计量学分析可明确不同产地药材制成的苓桂术甘汤之间的差异,为其内在质量评价提供参考。

基于网络药理学和分子对接技术探讨苓桂术甘汤改善非酒精性脂肪性肝病的潜在作用机制

目的:通过网络药理学和分子对接技术预测和探讨苓桂术甘汤改善非酒精性脂肪肝病的活性成分及其潜在的作用机制。方法:采用TCMSP、ETCM数据库筛选出苓桂术甘汤的活性成分和相关的潜在靶点。利用GeneCards数据库检索非酒精性脂肪肝病相关靶点。基于苓桂术甘汤潜在靶点与非酒精性脂肪肝病相关靶点的匹配结果,在STRING平台进行蛋白质相互作用分析,筛选核心靶点。利用CytoScape 3.9.1软件拓扑分析筛选出关键活性成分,构建苓桂术甘汤活性成分-非酒精性脂肪肝病-靶点-通路网络。通过Reactome与Metascape数据库进行基因本体论(GO)与京都基因与基因组百科全书(KEGG)富集分析。利用Autodock Tools 1.5.7将前5位核心靶点和对应的活性成分进行分子对接。结果:苓桂术甘汤改善非酒精性脂肪肝病的重点活性成分为槲皮素、柚皮素、山柰酚等,关键靶点有细胞肿瘤抗原p53(Cell Tumor Antigen p53,TP53)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1),主要涉及细胞对脂质的反应、对异种刺激的反应、无机物质反应等生物过程,主要富集在癌症通路、糖尿病并发症中的晚期糖基化终产物及其受体信号通路、白细胞介素-17信号通路等。TP53、TNF、IL-6、IL-1β与槲皮素对接良好,AKT1与柚皮素对接良好。结论:苓桂术甘汤可以多方向、多维度改善非酒精性脂肪肝病,本研究为进一步揭示苓桂术甘汤改善非酒精性脂肪肝病机制提供了理论基础和参考依据。

基于氧化应激及其相关凋亡蛋白研究苓桂术甘汤预处理对大鼠心肌缺血再灌注损伤的保护作用及机制

目的 基于氧化应激及其相关凋亡蛋白探讨苓桂术甘汤对大鼠心肌缺血再灌注损伤的保护作用及机制。方法 45只SPF级SD雄性大鼠,适应性喂养1周,随机分成假手术组(Sham组)、心肌缺血再灌注组(IR组)、苓桂术甘汤预处理组[IR+LGZG(0.68 g/kg)组],每组15只。依据组别灌胃给予相应药物预处理,1次/d,连续7 d。第8天通过结扎大鼠心脏冠状动脉左前降支(ligating the anterior descending, LAD),心肌缺血30 min后,进行缺血再灌注24 h, Sham组只做穿线处理不结扎,建立MIRI大鼠模型。造模成功后分别取各组大鼠的腹主动脉血清和心脏组织进行相关指标的检测。通过心电图观察心功能变化,通过TTC染色观察心肌梗死面积,通过HE染色观察心肌组织病理改变。采用生化和ELISA法检测心肌酶损标志物Tn-T、CK-MB、LDH含量。采用ELISA法检测血清中氧化应激指标SOD、MDA、GSH-Px含量。采用Western blot法检测心肌组织中的凋亡蛋白Bax、Caspase-3、Bcl-2含量。结果 与Sham组相比,IR组大鼠的心电图ST段向上拱起明显,心肌组织病理形态学发生改变,心肌梗死面积显著增加(P<0.01),血清中Tn-T、CK-MB、LDH浓度显著升高(P<0.01),SOD表达显著降低(P<0.01),MDA表达显著升高(P<0.01),心肌细胞中Caspase-3、Bax蛋白表达上调(P<0.01),Bcl-2表达下调(P<0.01);与IR组相比,IR+LGZG组可以减少MIRI所致心脏损伤(P<0.05),升高SOD的表达(P>0.05),降低MDA的表达(P<0.01),减少MIRI引起的心肌细胞凋亡(P<0.05)。结论 苓桂术甘汤对大鼠心肌缺血再灌注损伤治疗作用佳,其作用机制部分是通过抑制氧化应激和随后的心肌细胞凋亡来实现的。

基于网络药理学与分子对接探讨苓桂术甘汤治疗新冠肺炎合并支气管哮喘潜在作用机制研究

目的研究苓桂术甘汤治疗新型冠状肺炎合并支气管哮喘潜在的作用机制。方法基于TCMSP数据库筛选苓桂术甘汤主要活性有效成分。利用GeneCards、OMIM、DisgNET等数据库获取新冠肺炎和支气管哮喘疾病作用靶点。使用STRING数据库筛选核心靶点并构建蛋白网络互作分析,通过微生信对核心靶点进行GO和KEGG通路富集分析。借助Cytoscape3.7.1软件构建主要活性成分-靶点-信号通路的可视化处理。最后通过Autodocking 1.5.7将核心成分和核心靶点进行分子对接验证。结果苓桂术甘汤中含主要活性成分121个,支气管哮喘靶点共2115个,新冠肺炎靶点1972个,交集靶点58个,GO分析涉及细胞组成、细胞间信号调控和分子间蛋白结合;KEGG信号通路注释到AMPK通路、NF-kappa B通路、PI3K-Akt通路等152条信号通路。其中靶点IL6与槲皮素呈现出最低的亲和力为-7kcal/mol,TNF、IL6与槲皮素、山奈酚、β-谷甾醇结合能均小于-5 kcal/mol。结论本研究揭示了苓桂术甘汤通过多成分作用、多靶点、调节多条信号通路协同发挥对新冠肺炎合并支气管哮喘的治疗作用,为苓桂术甘汤的进一步分子机制研究提供理论依据。

周大勇治疗神经性耳鸣临证经验

神经性耳鸣是耳科最常见的一种耳鸣,其发病机制尚不明确,由于该病病因较为复杂,目前西医无法根治。周大勇主任医师运用中医治疗神经性耳鸣,在改善患者临床症状、疏导患者焦虑情绪方面具有较大优势。从辨证思路、治疗特色等方面系统阐述周老师治疗神经性耳鸣的学术思想与经验,周老师在临证施治上,运用“苓桂术甘汤”为基础方治疗神经性耳鸣,可有效缓解症状、提高生活质量,为临床诊治该病提供参考依据。附验案一则以资佐证。

基于网络药理学和分子对接探讨苓桂术甘汤治疗气道黏液高分泌状态作用机制研究

目的:基于网络药理学和分子对接技术探讨苓桂术甘汤治疗气道黏液高分泌状态(简称黏液高分泌)的作用机制。方法:使用中药系统药理学数据库与分析平台(TCMSP)检索苓桂术甘汤活性成分与靶点。通过GeneCards、OMIM数据库检索疾病靶点。基于Venny 2.1得到成分靶点与疾病靶点的交集。借助Cytoscape 3.7.2构建“药物-成分-靶点-疾病”网络图。通过STRING数据库建立交集靶点的蛋白质-蛋白质相互作用网络。使用David数据库对交集靶点进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。使用AutoDockTools 4.2.6和PyMOL 2.4.0进行核心靶点与其成分的分子对接。结果:筛选得到苓桂术甘汤120个活性成分,494个疾病靶点和75个交集靶点。主要活性成分包括檞皮素、山柰酚、光果甘草酮、芒柄花素和柚皮素等,关键靶点涉及前列腺素内过氧化物合酶2(Prostaglandin G/H Synthase 2,PTGS2)、雌激素受体1(Estrogen Receptor 1,ESR1)、过氧化物酶体增殖物激活受体γ(Peroxisome Proliferator-activated Receptor Gamma,PPARG)、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)14、激酶插入区受体(Kinase Insert Domain Receptor,KDR)等。由KEGG通路富集分析得到癌症通路、脂质和动脉粥样硬化、糖尿病并发症中的晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)信号通路、化学致癌-受体激活、卡波西肉瘤相关疱疹病毒感染等156条信号通路。分子对接结果表明核心靶点与其对应活性成分对接结果良好。结论:苓桂术甘汤具有多成分、多靶点、多通路协同治疗黏液高分泌作用。

苓桂术甘汤应用之我见

根据《伤寒论》与《金匮要略》相关记载,苓桂术甘汤功在温化痰饮,故对于当以痰饮停蓄为关键病机的心下逆满、心悸怔忡、眩晕、短气诸症具有较好的疗效。就临床实际而言,据此认识来使用本方,确实可以收到良好的治疗效果。只是因当前中医临证所遇患者,大多病情较久而复杂,故应用之时多需要结合具体病情,进行必要化裁。

真武汤合苓桂术甘汤化裁治疗糖尿病肾病肾阳虚型临床观察

目的:观察真武汤合苓桂术甘汤化裁治疗糖尿病肾病肾阳虚型的效果。方法:168例按照随机数字表法分为研究组和对照组各84例,对照组用卡托普利治疗,研究组用真武汤合苓桂术甘汤治疗。结果:研究组总有效率及免疫球蛋白A(IgA)、免疫球蛋白M(IgM)水平高于对照组(P<0.05),血清转化生长因子-β1(TGF-β1)、C反应蛋白(CRP)、白介素-6(IL-6)和血肌酐(SCR)、血尿素氮(BUN)、24h尿总量蛋白(TUP)水平以及不良反应发生率低于对照组(P<0.05)。结论:真武汤合苓桂术甘汤化裁治疗糖尿病肾病肾阳虚型效果较好,且安全。

苓桂术甘汤加减结合针刺方案在痰饮中阻型良性阵发性位置性眩晕治疗中的应用

目的分析苓桂术甘汤加减结合针刺方案治疗痰饮中阻型良性阵发性位置性眩晕(BPPV)的临床疗效。方法选取2021年8月至2022年8月齐齐哈尔市中医医院神经内科收治的80例痰饮中阻型BPPV患者作为研究对象,随机分为对照组与观察组,各40例。对照组基于常规西医治疗,观察组在对照组基础上联合苓桂术甘汤加减结合针刺治疗。比较两组临床疗效、中医症候积分、血液流变学指标、不良反应发生率及复发率。结果观察组治疗总有效率高于对照组(97.50%vs.80.00%,),差异有统计学意义(P<0.05)。治疗后,两组眩晕、视物旋转感、头重胸闷、肢体沉重、舌淡、苔白腻、脉弦滑积分均低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。治疗后,两组血浆黏度、全血黏度高切值、纤维蛋白原水平及红细胞聚集指数均低于治疗前,且观察组低于对照组,差异有统计学意义(P<0.05)。两组均未出现不良反应,观察组复发率低于对照组(0.00%vs.17.50%),差异有统计学意义(P<0.05)。结论苓桂术甘汤加减结合针刺方案治疗痰饮中阻型BPPV效果更佳,可降低中医症候积分,改善血液流变学指标,且不会增加不良反应,复发率较低。

基于网络药理学探讨苓桂术甘汤治疗慢性心力衰竭的作用机制

目的:基于网络药理学方法筛选苓桂术甘汤的活性成分及核心靶标,进一步探讨其防治慢性心力衰竭(Chronic Heart Failure,CHF)潜在分子机制。方法:在中药系统药理学数据库与分析平台(TCMSP)检索苓桂术甘汤的活性成分,并预测活性成分作用靶点,采用GeneCards数据库筛选CHF的疾病靶点,运用R语言软件筛选药物与疾病的共同靶点,应用Cytoscape3.7.2软件构建药物活性成分-疾病靶点相互作用网络,应用STRING 11.0构建共同靶点蛋白质相互作用网络,并用Cytoscape3.7.2对蛋白质-蛋白质相互作用网络进行拓扑分析,R语言软件对共同靶点进行基因本体论富集分析、京都基因与基因组百科全书(KEGG)通路富集分析,同时应用Cytoscape 3.7.2软件构建KEGG通路与富集蛋白的相互作用关系网络。结果:获得苓桂术甘汤有效生物活性成分95个,与CHF相关的靶点有72个,这些靶点主要涉及对营养水平的反应、对脂多糖的反应、循环系统中的血管过程、对活性氧的反应等生物学过程,并主要富集在糖尿病并发症中的晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)、流体剪切应力与动脉粥样硬化、肿瘤坏死因子等信号通路上,富集核心靶点蛋白主要有丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)1、MAPK14、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、基质金属蛋白酶9、血管内皮生长因子A等。结论:苓桂术甘汤防治CHF具有多成分、多靶点、多途径的作用特点,并推测了其治疗CHF的潜在作用机制,为进一步研究其治疗CHF的药效物质基础提供一定的理论依据。

加味苓桂术甘汤治疗糖尿病前期临床观察

目的:观察加味苓桂术甘汤治疗糖尿病前期(脾虚痰湿证)的临床疗效及对患者血糖、血脂变化的影响。方法:将60例符合临床观察条件的患者随机分为治疗组、对照组两组,两组30例。两组患者均同样予以糖尿病饮食、适当运动等基础治疗措施,对照组患者给予口服二甲双胍缓释片治疗,治疗组患者在对照组基础上服用加味苓桂术甘汤治疗。两组患者在性别、年龄、病程、体质量指数、实验室检验指标、中医证候等方面差异均无统计学意义(P> 0.05),临床观察疗程均为28 d。结果:治疗后治疗组患者总有效率为93.33%(28/30),对照组患者总有效率为83.33%(25/30),总疗效及改善证候等的差异具有统计学意义(P <0.05)。与对照组患者相比较,治疗组患者治疗后空腹血糖(Glucose,GLU)、餐后2 h血糖(2-hour Plasma Glucose,2 h PG)、总胆固醇(Total Cholesterol,TC)、低密度脂蛋白胆固醇(Low-density Lipoprotein Cholesterol,LDL-C)均明显下降,差异具有统计学意义(P <0.05)。结论:糖尿前期患者存在程度不同的脾阳虚痰湿阻遏等状态,单纯西药治疗效果较差,联合中医药辨证治疗可以显著提高临床疗效及改善患者症状,调节血糖、血脂等。加味苓桂术甘汤为中医经方加减,治疗糖尿病前期患者(脾虚痰湿证)的临床疗效优于单纯西药,并且能够明显改善患者临床症状,降低血糖、血脂等,值得在临床上进一步推广应用。

Linggui Zhugan Decoction(苓桂术甘汤)Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Mice by Suppressing TGF-β1 Smad Signaling Pathway

Objective:To investigate the inhibitory effect of Linggui Zhugan Decoction(LZD,苓桂术甘汤)on the ventricular remodeling(VR)after acute myocardial infarction(AMI)and related mRNA and proteins expression in transforming growth factor-beta 1(TGF-β1)/Smad signaling pathway,and explain its putative mechanism.Methods:A VR model was generated by ligation of coronary artery in mice.Two weeks after surgery,60 mice were randomly divided into the model group,the sham-operation group(distilled water),the positive control group(2.4 mg/kg simvastatin),and the low-,medium-and high-dose LZD groups(2.1,4.2,8.4 g crude drug/kg,respectively)by a random number table,10 mice in each group.Mice in each group was treated for 4 weeks.Changes of hemodynamics indices and cardiac weight index were detected by the PowerLab data acquisition and analysis recording instrument.Morphology changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining.The expressions of TGF-β1,Smad2,Smad3,p-Smad2 and p-Smad3 in myocardial tissue were detected by Western blotting.The mRNA expressions of TGF-β1,Smad2 and Smad3 were detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR).The expressions of matrix metalloprotein 2(MMP2),MMP9,collagenⅠand collagen Ⅲ were observed by immunohistochemical methods.Results:VR mice showed significant dysfunction in hemodynamic indices and cardiac structure and function.Compared with the shamoperation group,myocardial tissue damage,interstitial fibrosis occurred in the model mice,left ventricular systolic pressure(LVSP),left ventricular pressure maximum contraction rate(+dp/dtmax)and left ventricular pressure maximum relaxation rate(-dp/dtmax)decreased significantly(all P<0.01),while left ventricular end-diastolic pressure(LVEDP),cardiac weight index and left ventricular weight index elevated significantly,meanwhile TGF-β1,p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagen Ⅰ,collagen Ⅲ protein expressions in myocardial tissue and TGF-β1 Smad2 and Smad3 mRNA expressions increased significantly(all P<0.01).Compared with the model group,LZD could significantly improve the pathological changes of myocardial tissue,increase LVSP,+dp/dtmax and-dp/dtmaxf lower LVEDP,reduce the whole heart weight index and left ventricular weight index and inhibit the over-expressions of TGF-β1f p-Smad2,p-Smad3,Smad2,Smad3,MMP2,MMP9,collagenⅠand collagenⅢproteins in myocardial tissue and mRNA expressions of TGF-β1 Smad2 and Smad3(P<0.05 or P<0.01).Conclusion:LZD can significantly suppress VR induced by AMI,and its underlying mechanism may be associated with its inhibitory effect on the TGF-β1/Smad signaling pathway.

Protective effects of Modified Linggui Zhugan Decoction combined with short-term very low calorie diets on cardiovascular risk factors in obese patients with impaired glucose tolerance

OBJECTIVE:To observe the protective effects of modified Linggui Zhugan Decoction combined with short-term very low calorie diets(VLCDs) on cardiovascular risk factors in obese patients with impaired glucose tolerance(IGT).METHODS:Eighty-five obese patients with IGT of spleen hypofunction and dampness accumulation type were randomly divided into treated group(n=45)and control group(n=40).The treated group was given Linggui Zhugan Decoction combined short-term VLCDs.The control group was given basic weight-reduction treatment.The total course was 6 months.Changes of fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS),lipid metabolism,blood pressure,body mass index(BMI) and waist circumference(WC) were observed,and the outcomes were reviewed after the treatment.RESULTS:Compared with the control group,the levels of FPG,2hPG,HbA1c,FINS,HOMA-IR decreased significantly(P<0.05),and the indexes of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL),systolic blood pressure(SBP),diastolic blood pressure(DBP),BMI and WC were improved significantly(P<0.05) in the treated group.The transformation rate of normal glucose tolerance(NGT) was higher in treatment group than control group(P<0.01).No severe adverse reaction was found in the therapeutic course.CONCLUSION:The modified Linggui Zhugan Decoction combined with short-term VLCDs has good protective effects on cardiovascular risk factors as a treatment intervention for IGT with obesity,as it could improve glycometabolism,significantly decrease the levels of blood pressure,blood lipids,BMI,WC and effectively cut-off and reverse the development of diabetes mellitus.

Effects of the Modified Linggui Zhugan Decoction(加味苓桂术甘汤) Combined with Short-term Very Low Calorie Diets on Glycemic Control in Newly Diagnosed Type 2 Diabetics

Objective:To evaluate the effects of the modified Linggui Zhugan Decoction(加味苓桂术甘汤) combined with short-term very low calorie diets(VLCDs) on glycemic control in newly diagnosed type 2 diabetes mellitus(T2DM) patients.Methods:A total of 20 subjects with newly diagnosed T2DM were treated with the modified Linggui Zhugan Decoction(one-month administration) combined with short-term VLCDs(5 days),and 3-months follow-up.A standard 75-g oral-glucose-tolerance test(OGTT) indexes fasting plasma glucose(FPG),post-prandial 0.5 h and 2 h plasma glucose(P0.5hPG,P2hPG),glycated hemoglobin A1C(GHbA1C),body weight,body mass index(BMI),insulin function,insulin resistance index,incidence of hypoglycemia,and the liver and renal functions were evaluated before and after treatment.Correlations of BMI with insulin function and insulin resistance were also assessed.Results:After the treatment,the patients' plasma glucose decreased steadily,FPG decreased from 5.8±0.9 mmol/L at pre-treatment to 5.0±0.6 mmol/L at 3-months follow-up(P<0.05),and P2hPG decreased from 11.7±3.8 mmol/L at pre-treatment to 6.9±0.9 mmol/L at 3-months follow-up(P<0.01).The level of GHbA1C declined from(6.47±1.24)% at pre-treatment to(6.14±0.99)% at 3-months follow-up(P<0.01).Body weight and BMI also declined significantly.Insulin resistance index was improved obviously and no event of hypoglycemia occurred.Part of the patients companied with fatty liver had a transient increase in hepatic transaminase during the treatment,but it turned to normal after the treatment.Conclusions:The modified Linggui Zhugan Decoction combined with short-term VLCDs can be safely implemented for steady glycemic control in newly diagnosed T2DM patients.

苓桂术甘汤对压力负荷致心衰小鼠心功能、肠道屏障和菌群的影响

目的:探讨苓桂术甘汤对心力衰竭小鼠心功能、肠道屏障和菌群的影响。方法:采用主动脉弓缩窄术(transverse aortic constriction,TAC)复制心衰小鼠模型,术后1周,将小鼠随机分为假手术组(Sham,n=7)、TAC模型组(TAC,n=7)、苓桂术甘汤低剂量组(LD-L,n=6,4.29 g/kg)和苓桂术甘汤高剂量组(LD-H,n=7,8.58 g/kg),每日灌胃给药共8周。采用小动物超声、Western blot和16S rRNA高通量测序分别检测小鼠心功能、结肠组织中ZO-1及Occludin蛋白表达、粪便菌群。结果:与Sham组比较,TAC小鼠左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)显著升高;射血分数(EF)、短轴缩短率(FS)和ZO-1、Occludin蛋白表达显著降低。与TAC组比较,苓桂术甘汤治疗组能显著降低LVEDD、LVESD,升高EF、FS,上调ZO-1、Occludin蛋白表达。16S rRNA测序结果显示,与Sham组比较,TAC组小鼠肠道细菌丰度和多样性降低,苓桂术甘汤治疗组可以增加心衰小鼠肠道细菌丰度和多样性,调节肠道细菌结构紊乱,增加与短链脂肪酸产生密切相关的菌属如norank_f_Muribaculaceae、Prevotellaceae_NK3B31_group的丰度。结论:苓桂术甘汤可以显著改善心衰小鼠的心功能,修复肠黏膜屏障,调节肠道细菌结构紊乱,促进短链脂肪酸产生相关菌的生长。