Introduction: Hepatic steatosis is a hepatic pathological change closely associated with metabolic disorders, commonly observed in various metabolic diseases such as metabolic syndrome (MetS), with a high global prevalence. Dai-Zong-Fang (DZF), a traditional Chinese herbal formula, is widely used in clinical treatment for MetS, exhibiting multifaceted effects in reducing obesity and regulating blood glucose and lipids. This study aims to explore the mechanism by which DZF modulates the gut microbiota and reduces hepatic steatosis based on the gut-liver axis.Methods: This study utilized db/db mice as a disease model for drug intervention. Body weight and fasting blood glucose were monitored. Serum lipid and transaminase levels were measured. Insulin tolerance test was conducted to assess insulin sensitivity. Hematoxylin and eosin (HE) staining was employed to observe morphological changes in the liver and intestine. The degree of hepatic steatosis was evaluated through Oil Red O staining and hepatic lipid determination. Changes in gut microbiota were assessed using 16S rRNA gene sequencing. Serum lipopolysaccharide (LPS) levels were measured by ELISA. The expression levels of intestinal tight junction proteins, intestinal lipid absorption-related proteins, and key proteins in hepatic lipid metabolism were examined through Western blot and RT-qPCR.Results: After DZF intervention, there was a decrease in body weight, alleviation of glucose and lipid metabolism disorders, reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and mitigation of insulin resistance in mice. DZF significantly modulated the diversity of the gut microbiota, with a notable increase in the abundance of the Bacteroidetes phylum. PICRUSt indicated that DZF influenced various functions in gut microbiota, including carbohydrate and amino acid metabolism. Following DZF intervention, serum LPS levels decreased, intestinal pathological damage was reduced, and the expression of intestinal tight junction protein occludin was increased, while the expression of intestinal lipid absorption-related proteins cluster of differentiation 36 (CD36) and apolipoprotein B48 (ApoB48) were decreased. In the liver, DZF intervention resulted in a reduction in hepatic steatosis and lipid droplets, accompanied by a decrease fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) and fatty acid transport protein 2 (FATP2). Conversely, there was an increase in the expression of the fatty acid oxidation-related enzyme carnitine palmitoyltransferase-1𝛂 (CPT-1𝛂).Conclusion: DZF can regulate the structure and function of the intestinal microbiota in db/db mice. This ameliorates intestinal barrier damage and the detrimental effects of endotoxemia on hepatic metabolism. DZF not only inhibits intestinal lipid absorption but also improves hepatic lipid metabolism from various aspects, including de novo lipogenesis, fatty acid uptake, and fatty acid oxidation. This suggests that DZF may act on the liver and intestine as target organs, exerting its effects by improving the intestinal microbiota and related barrier and lipid absorption functions, ultimately ameliorating hepatic steatosis and enhancing overall glucose and lipid metabolism.
中土主运化饮食水谷,升清降浊,是人体代谢之核心.调节机体代谢的重要器官之一为脂肪组织,其生理、病理与中土运化关联紧密.能量过剩引起脂质沉积,脂肪组织过度肥大,继发脂解、胰岛素抵抗,可致糖脂代谢紊乱.糖原周转是最新发现的一种脂肪组织代谢途径,可促进白色脂肪棕色化,调节机体产热和能量消耗,从而改善代谢.中土不运,清浊失常是肥胖、糖尿病等糖脂代谢紊乱疾病的常见病机,斡旋中土枢机以调和阴阳为主要治则.中土调运则精微得以正化,消减膏浊之积.黄连在代谢性疾病的治疗中应用广泛,其气寒味苦,行"中土之制"而清中土湿热浊邪痞结,配伍组方常围绕"中土之制",从"辛开苦降""苦寒直折"及"寒热并用"等展开.
从"阳化气、阴成形"的视角重新认识肥胖症的成因,并将现代分子生物学机制与传统中医理论结合,梳理探讨"转静为动、化形为气"理念在肥胖症辨治中的应用.形气理论指导下的中医方药内涵分为补气化形使精微归于正化、益火之源以消阴翳之形、苦辛开结以畅气调形3个方面,均围绕激活脂肪产热的核心机制,发挥改善肥胖症的作用.
Graves眼病是弥漫性毒性甲状腺肿最常见、最复杂的并发症,Graves眼病的基本病机为郁火之邪上炎眼目,因此郁火理论在Graves眼病病理改变方面有着重要应用.Graves眼病眼睑征乃脾营亏虚,中焦气机郁遏生火上炎所致;眼眶结缔组织增生乃痰浊湿滞,壅塞生火灼目所致;球结膜充血和水肿乃瘀血阻于眼络,郁热不得布散所致;泪膜功能下降,角膜炎症或溃疡穿孔乃肾阴不足,相火离位上扰所致;脉络膜及视网膜血流改变乃肝气怫郁于内,日久化火所致.基于郁火与眼部病理改变的理论联系,在治疗方面,可采用局部辨证与整体辨证相结合的方式,使用益营散火、化形解火、培肾透火、理气清火等治法,以达到疏解郁火,宣畅气机之效.
The application scope of classical famous prescription Xiayuxue Decoction was discussed and expanded based on the analysis of the formula indications. It is thought that blood stasis is the cause of indications of Xiayuxue Decoction, and blood stasis stagnating in the lower energizer is its pathogenesis, which should be distinguished from general blood stasis. The connotation of the Decoction can be explained from four points: firstly herbs with drastic downward-expelling effect can attack blood stasis and herbs with stasis-breaking effect can promote the generation of new blood; secondly the orderly ascending and descending movement of herbal action can dredge collaterals; thirdly the combination of herbs with drastic and mild properties, reducing and nourishing functions can neutralize the strong attacking-expelling side effect; and fourthly the worm medicine can penetrate deeply into the place where the pathogen ambushes. One proven case is provided.
ObjectivePrevious studies have reported different opinions regarding the association between abdominal obesity and diabetic retinopathy (DR) in patients with diabetes mellitus (DM). In this study, we aimed to investigate this problem through a systematic review and meta-analysis to provide a basis for clinical interventions.MethodsA comprehensive search was conducted in the PubMed, Embase, and Web of Science databases up to May 1, 2022, for all eligible observational studies. Standardized mean differences (SMD) and 95% confidence intervals (CI) were evaluated using a random-effects model in the Stata software. We then conducted, publication bias assessment, heterogeneity, subgroup and sensitivity analyses.ResultsA total of 5596 DR patients and 17907 non-DR patients were included from 24 studies. The results of the meta-analysis of abdominal obesity parameters showed statistically significant differences between DR and non-DR patients in both type 1 and type 2 diabetes. Waist circumference (WC) was higher in patients with DR than in the non-DR patients. In the waist-hip ratio (WHR) subgroup, the level of WHR was higher in patients with DR than that in non-DR patients. The association between abdominal obesity and mild to moderate nonproliferative DR or vision-threatening DR groups did not show any statistical difference. Subgroup analysis according to ethnicity showed that Caucasians had higher levels of combined abdominal obesity parameters than Asians.ConclusionWe found that abdominal obesity measured by WC and WHR is associated with DR in patients with type 1 and type 2 diabetes. This association is stronger in Caucasians than in Asians, where isolated abdominal obesity might be more related to DR. However, no correlation was found between abdominal obesity and varying degrees of diabetic retinopathy. Further prospective cohort studies with larger sample sizes are yet to be conducted to clarify our findings.
Introduction: The global prevalence of obesity is rising rapidly. Conversion of white adipose tissue (WAT) into beige adipose tissue with heat-consuming characteristics, i.e., WAT browning, effectively inhibits obesity. Dai-Zong-Fang (DZF), a traditional Chinese medicine formula, has long been used to treat metabolic syndrome and obesity. This study aimed to explore the pharmacological mechanism of DZF against obesity.Methods:In vivo, C57BL/6J mice were fed high-fat diets to establish the diet-induced obese (DIO) model. DZF (0.40 g/kg and 0.20 g/kg) and metformin (0.15 g/kg, positive control drug) were used as intervention drugs for six weeks, respectively. The effects of DZF on body size, blood glucose and lipid level, structure and morphology of adipocytes and browning of inguinal WAT (iWAT) in DIO mice were observed. In vitro, mature 3T3-L1 adipocytes were used as the model. Concentrations of DZF (0.8 mg/mL and 0.4 mg/mL) were selected according to the Cell Counting Kit-8 (CCK8). After 2d intervention, lipid droplet morphology was observed by BODIPY493/503 staining, and mitochondria number was observed by mito-tracker Green staining. H-89 dihydrochloride, a PKA inhibitor, was used to observe the change in browning markers′ expression. The expression levels of browning markers UCP1 and PGC-1α and key molecules of PKA pathway were detected in vivo and in vitro.Results:In vivo, compared with vehicle control group, 0.40 g/kg DZF significantly reduced obesity in DIO mice from body weight, abdomen circumference, Lee′s index, and WAT/body weight (p < 0.01 or p < 0.001). 0.40 g/kg DZF also significantly reduced fasting blood glucose (FBG), serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (p < 0.01 or p < 0.001). The iWAT′s morphology and mitochondria were browning after DZF intervention. In HE-staining, the lipid droplets became smaller, and the number of mitochondria increased. The mitochondrial structure was remodeled under the electron microscope. The expression of UCP1, PGC-1α and PKA was elevated in iWAT detected by RT-qPCR (p < 0.05 or p < 0.001). In vitro, compared with the control group, 0.8 mg/mL DZF intervention significantly increased the number of mitochondria and expression of UCP1, PGC-1α, PKA, and pCREB (p < 0.05 or p < 0.01). In contrast, UCP1 and PGC-1α expression were significantly reversed after adding PKA inhibitor H-89 dihydrochloride.Conclusion: DZF can promote UCP1 expression by activating the PKA pathway, thereby promoting browning of WAT, attenuating obesity, and reducing obesity-related glucose and lipid metabolism abnormalities, indicating that DZF has the potential to be selected as an anti-obesity drug to benefit obese patients.
甲状腺功能亢进症是一种多发于青年人群、以乏力消瘦及心悸多汗等高代谢证候群为主要表现的内分泌疾病.现代医家多从心肝火旺、心肾阴虚等为切入点治疗甲状腺功能亢进症.刘喜明教授中医功底深厚,临证三十余载,对内分泌系统疾病有着丰富的临床经验,尤其在对甲状腺功能亢进症认识及用药方面有自己独到见解.刘教授结合古籍文献记载及个人临床经验,认为甲状腺功能亢进症发病除心肝肾外,亦当从脾阴虚立论.刘教授明确脾阴虚的本质为气阴两虚,从解剖、病理、临床症状、脾与四脏关联性等角度总结脾阴虚与甲状腺功能亢进症发病密切相关,提出益气健脾,养阴清热的基本治法及"甘淡合酸微寒"的基本用药法则,主张药用莲子肉、白扁豆、薏苡仁等"甘淡平和以益营气"、白芍、麦冬、五味子等"甘酸微寒以滋营阴",为甲状腺功能亢进症的治疗提供新方法、新思路.
甲状腺功能亢进症可合并多种并发症,其中以重症肌无力较为严重.本案患儿确诊为甲状腺功能亢进合并重症肌无力,其证候复杂、病情较重、治疗难度大.中医学认为本案瘿病为气郁生火,耗伤阴液,虚热蒸炽;痿证则属元亏气陷,中焦不足而肌肉失养.二证互相影响,共成此病.临床可以"气陷阴中"为机,升元益阴为法辨治,治疗收效良好.
高热是临床常见症状,其病因错综复杂,属危重症范畴,中医在退热方面有天然的优势.但中医多种证型均可能出现高热症状,针对不同的证型,应当仔细思辨,分而治之.本文从中医辨证入手,从阴分郁热、伏暑晚发、阳气亏虚、邪伏少阳四个角度出发分析讨论,并附有治疗妇女经前高热、儿童感冒高热、老年高热、青年亚急性甲状腺炎高热的临床验案,以示其临床思路.
复发性甲状腺功能亢进症是甲状腺功能亢进症的一种特殊类型,其特点是在疾病治愈之后反复发作,给患者造成了严重的生理及心理困扰.中医学认为复发性甲状腺功能亢进症与情志失调密切相关.君火、相火共同参与情志调节,维系情志活动正常进行.反之,情志不畅可以导致君相失衡.朱丹溪提出"心动则相火动",心君易受外物扰动,心君不安致使心火亢盛,从而导致相火妄动,本团队认为这是复发性甲状腺功能亢进症的核心病机.此外,复发性甲状腺功能亢进症病程日久,以肝肾阴虚为主,而相火得肝肾之阴滋养,阴液亏虚则相火更易妄动.在治疗方面,首当从调畅情志入手,重视心理情志疗法及传统功法的运用;其次宁熄君相火旺,以期恢复君相平衡,育阴之法当贯彻始终.具体选方用药,首先以质柔缓静之品为基础制亢阳;再根据受累脏腑不同,选择相应脏腑归经之品对症加减,而后按照性味合化配伍,泻火护阴;最后注意益气扶正,顾护正气.
目的:分析2型糖尿病肾病(T2DN)db/db小鼠的中医证候演变规律,为db/db小鼠在中医药干预T2DN研究中的应用提供依据.方法:建立中医证候表征体系,采集并分析8~20周龄db/db小鼠及同窝野生型小鼠的中医证候表征信息,包括形体、活动、二便、舌色、进食、体质量、空腹血糖(FBG)、血脂、24 h尿量、尿微量白蛋白排泄等.结果:8~14周龄db/db小鼠形体肥胖,大便秘结,活动少,力量小,进食量、体质量、FBG、24 h尿量及尿微量白蛋白排泄逐渐增加,舌质红,符合消渴病早期阳明热盛的证候特点,兼有痰湿、气虚证表现;14~16周龄db/db小鼠纳食减少,体质量、尿微量白蛋白排泄增加,符合脾气亏虚、痰湿蕴阻的证候特点;16~20周龄db/db小鼠进食量、体质量、24h尿量下降,FBG及尿微量白蛋白排泄持续增加,血脂水平高,部分小鼠出现精神萎靡、蜷缩喜卧等表现,符合消渴病中后期脾肾亏虚、气阴两虚的证候特点,兼有肾阳虚、痰湿证表现.结论:本实验中,8~20周龄db/db小鼠T2DN的中医证候演变符合"实则阳明,虚则太阴,久病及肾"的病机转变特点.其中,8~14周龄db/db小鼠以阳明热盛证为主,兼有痰湿、气虚证;14~16周龄db/db小鼠以脾气亏虚、痰湿阻滞证为主;16~20周龄db/db小鼠以气阴两虚、脾肾亏虚证为主,兼有肾阳虚、痰湿证.
文章介绍刘喜明教授应用瓜蒌桂枝汤治疗类风湿关节炎的经验.在中医理论中,类风湿关节炎属于痹病的范畴.刘教授认为痹病与营卫关系密切,其病机可体现为营阴不足、外邪痹阻,营阴不足不能濡养筋骨关节,外邪内侵与经脉相合而作痹病.治疗上以益阴调营、透邪通痹为法,通过补益营阴、濡养筋脉,调和营卫使气血周流,使邪无所痹.瓜蒌桂枝汤是益阴和营、调和阴阳的代表方剂,在此方为基础上进行加减变法,使其具有益液舒筋、透邪通痹的作用,从而可以治疗营血不足、外邪痹阻的类风湿关节炎.
安宫牛黄丸是中医治疗热闭急症的"凉开三宝"之一,是中医经典的丸药代表.现代文献资料研究发现,安宫牛黄丸的临床运用范围宽泛.但关于安宫牛黄丸的源流及历史沿革尚待梳理与明确.本文通过查阅及分析相关文献,论证安宫牛黄丸的祖方始于明代万全《痘疹世医心法》中所载的牛黄清心丸,并非《太平惠民和剂局方》中的牛黄清心丸,清代叶天士在万氏之法上有所增补,最终吴鞠通继承叶氏思想,成方定于《温病条辨》.
目的:基于网络药理学探讨"白术-茯苓"治疗代谢综合征(metabolic syndrome,MS)的作用机制.方法:结合中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)和文献检索,筛选"白术-茯苓"药对的活性成分.通过PharmMapper数据库预测各成分作用靶点,并使用Universal Protein(UniProt)数据库规范靶点名称.从人类基因数据库(GeneCards)、治疗靶标数据库(therapeutic target database,TTD)、Dis-GeNET三个数据库中筛选MS相关靶点后,与"白术-茯苓"各成分作用靶点合并取交集得到"白术-茯苓"治疗MS的潜在靶点,导入Cytoscape 3.7.2软件构建"药物-成分-靶点"网络.通过String平台和Cytoscape软件构建蛋白质互相作用网络,并用插件CytoHubba筛选核心靶点.用R软件对"白术-茯苓"治疗MS的潜在靶点进行基因本体(gene ontol-ogy,GO)分子功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析.结果:筛选得到"白术-茯苓"活性成分26种,治疗MS的重要成分为茯苓新酸A、14-乙酰基-12-千里光酰基-8-顺式白术三醇、茯苓新酸B、7,9(11)-去氢茯苓酸、茯苓新酸C等;潜在治疗靶点47个,核心靶点包括血清白蛋白(albumin,ALB)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、丝裂原活化蛋白激酶 1(mitogen-activated protein kinase 1,MAPK1)、雌激素受体1(estrogen receptor,ESR1)、MAPK8、MAPK14等;分子功能主要涉及调节类固醇激素受体活性、类固醇结合、核受体活性等;信号通路主要涉及雌激素信号通路、晚期糖基化终产物及其受体(advanced gly-cation end product-receptor,AGE-RAGE)信号通路、叉头转录因子(forkhead box 0,FoxO)信号通路、受体酪氨酸激酶(receptor tyrosine-protein kinase,ErbB)信号通路、白细胞介素-17(interleukin17,IL-17)信号通路等.结论:"白术-茯苓"药对可通过多成分、多靶点、多途径发挥对MS的治疗作用,为实验研究提供一定理论参考.
目的 观察中药代综方对棕榈酸(Palmitic acid,PA)诱导胰岛素抵抗(Insulin resistance,IR)的3T3-L1脂肪细胞中细胞因子瘦素、抵抗素、肿瘤坏死因子α(Tumor necrosis factor-α,TNF-α)的影响.方法 采用传统"鸡尾酒式"诱导3T3-L1前脂肪细胞分化成熟,用0.5 mmol/L PA建立IR模型.分为空白对照组、模型组、代综方低浓度组(含代综方生药量0.5 mg/ml)、代综方高浓度组(含代综方生药量2.0 mg/ml),干预48 h.葡萄糖氧化酶法检测培养上清中的葡萄糖浓度,计算葡萄糖基础消耗量(GBasic)和胰岛素刺激下消耗量(GIns),评价胰岛素敏感性指数(ISI).ELISA检测上清中瘦素、抵抗素、TNF-α的含量,Real-Time PCR检测瘦素、抵抗素、TNF-α的mRNA表达.结果 与空白对照组比较,模型组GIns、ISI均明显降低(P<0.01);与模型组比较,代综方高、低浓度组GBasic、GIns、ISI均明显升高(P<0.05,P<0.01),且代综方高浓度组GBasic、GIns、ISI较代综方低浓度组明显升高(P<0.05,P<0.01);与模型组比较,代综方高浓度组3T3-L1脂肪细胞上清中瘦素的含量明显增加(P<0.01),且抵抗素、TNF-α的含量明显减少(P<0.05,P<0.01);与模型组比较,代综方高浓度组3T3-L1脂肪细胞瘦素mRNA表达水平明显升高(P<0.01),且代综方低浓度和高浓度组抵抗素、TNF-αmRNA表达水平均明显降低(P<0.05,P<0.01).结论 代综方能够增加PA诱导的IR脂肪细胞葡萄糖消耗,提高胰岛素敏感性,同时上调瘦素水平,降低抵抗素、TNF-α水平.
Graves病患者甲状腺血流丰富,存在大量血管新生.中医认为,"痰"凝结于颈前,日久不消,为病之"宿根",是Graves病反复发作、经久不愈的关键,化痰散结应为Graves病的核心治法,贯穿治疗始终.夏枯草是中医治疗Graves病的常用中药,具有抑制血管新生的作用,含夏枯草中药复方可以降低Graves病患者血清中血管内皮生长因子水平,该作用可能是夏枯草治疗Graves病的主要作用机制.
医籍文献中清浊概念广泛存在"同词异义"现象,因不同取象来源构建的清浊概念具备不同的内涵.取象于天地生成意象的清浊观念,以升降属性为核心特征,后世升清降浊治法、谷气清浊体系、宣清导浊学说等分支理论或由此发展而来.取象于水流动静意象的清浊观念,则以动静属性为核心特征,继而演变出营卫清浊、病机清浊等学说.而中药药性认知也因受取象比类的清浊理论影响,形成了以质重味厚主降者为浊和以辛香雄烈主动者为浊的两种特色鲜明的药性清浊理论.
Graves眼病病机为火热之邪郁滞眼目气机,此"火"有阳有阴,阳火乃肝失条达,气机郁结而生,阴火乃脾营不荣,阳气郁滞所致,火邪常与有形之邪搏结,顽固缠绵.临床应以"发"为治疗原则,善用风药,宣发各经郁热;审证求因,阳火清透之,阴火补散之;重视眼目局部辨证,祛除有形之邪,如此可使气机出入畅达,升降顺条,眼目可明矣.
从中医学视角来看,甲状腺多气多血,其生理功能有赖于血脉的重要作用.认为甲状腺血脉功能异常引起Graves病的发生,其主要病理因素为火、痰、瘀,而火、痰、瘀的产生与甲状腺血管新生密切相关.中医治疗Graves病的基本方法均与调血脉之法密切相关,药理研究亦表明,夏枯草、土贝母等常用于治疗Graves病的中药具有抑制血管新生的作用,因此抑制甲状腺血管新生可能是调血脉之法治疗Graves病的作用机制之一.