
Prostate diseases,male infertility,sexual dysfunction and other male diseases are highly prevalent in men and seri-ously affect their quality of life,causing significant impacts on their physical and mental health.According to the theory of"brain-heart-kidney-essence chamber(BHKE)"axis,the brain,heart,kidney and essence chamber are linked by meridians,based on es-sence and blood,and guided by spirit,which are interconnected to form an organic whole as the main axis for the pathogenesis,diag-nosis and treatment of male diseases.At present,considerable progress has been made in the application and development of the"BH-KE"axis theory in the treatment of male diseases in Chinese medicine,but the interpretation of its scientific connotation is not suffi-cient enough and its biological basis lacks further clarification.This review explores into the biological basis of the maladjusted BHKE axis in different male diseases,such as chronic prostatitis,BPH,male infertility,ED,premature ejaculation,from the perspectives of the nerves,endocrine,immune system,and micro-environment,aiming to provide some evidence for further in-depth studies of the scientific connotation and application value of the"BHKE"axis theory in the treatment of male diseases.
Background To implement the spirit of the 20th National Congress of the Communist Party of China and the Opinions on Promoting the Inheritance, Innovation, and Development of Traditional Chinese Medicine (TCM), regularly summarize the research results of TCM, present the academic progress on TCM dynamically, and fully leverage the academic leadership of academic groups, the China Association of Chinese Medicine organized the selection of the top 10 academic progress on TCM in 2022. The selection process adhered to 4 orientations, eliminated any biases, highlighted the solutions to clinical problems, answered scientific questions, and led the industry’s development. It reflected an exploratory and forward-looking approach, emphasizing innovation and breakthroughs. The selection focused on new laws, new discoveries, new methods, new products, and new theories in the field of basic research and applied basic research in TCM. Through a process of dynamic collection, preliminary examination, review, and final judgment, the top 10 academic progress of TCM in 2022 were determined.
Background: No comprehensive meta-analysis has evaluated the efficacy and safety of the protective effect of Jiedu Tongluo Therapy on the kidney of DKD until now. This meta-analysis covers this gap in knowledge. Methods: We have conducted an extensive search of databases, including CNKI, Wanfang, PubMed, and Web of Science. The selection was based on conventional treatment, including information and education on DKD, blood glucose, hypertension control methods, and lifestyle. The control group was composed of conventional western medicine or proprietary Chinese medicine, and the experimental group was composed of Jiedu Tongluo therapy controlled trials (RCTs) between 2003 and 2023. R 4.1.0 software was used to perform statistical analysis. Results: A total of 1871 patients from 19 RCTs were analyzed. Meta-analysis results showed that the Jiedu Tongluo therapy was effective in improving clinical efficacy (OR = 2.47, 95% CI [1.94, 3.15], I 2 = 0%), and these trials were more effective in reducing Scr (MD = -19.81, 95% CI [-27.64, -11.97], p < 0.01), BUN (MD = -0.70, 95% CI [-1.13, -0.27], p < 0.01), UAER (MD = -29.97, 95% CI [-37.33, -22.61], p < 0.01), FBG (MD = -0.85, 95% CI [-1.22, -0.47], p < 0.01), and certain medication safety (OR = 0.75, 95% CI [0.27, 2.11]). Conclusions: For treating diabetic kidney disease, TCM-based Jiedu Tongluo therapy showed optimal clinical efficacy and safety. However, further rational experiments are needed to validate the above conclusions.
溃疡性结肠炎(UC)主要发生于结直肠,该病病理机制复杂,与肠道的不可控性炎症反应密切相关.当前,西医主要使用糖皮质激素、免疫抑制剂等减轻肠道炎症,虽然可以在一定程度上阻遏UC的进展,但不良反应较大.越来越多研究证实,中医药防治UC具有明显的优势,可显著降低该病复发率.细胞焦亡是一种新型细胞死亡方式,可破坏细胞结构,释放胞内促炎物质,介导UC肠道免疫反应.研究人员认为中医药对细胞焦亡的干预主要表现为促进细胞焦亡(损其有余)和抑制细胞焦亡(补其不足),这与调节阴阳相一致.其中,中药主要通过抑制细胞焦亡(补其不足),减轻肠道免疫反应,起到治疗UC的作用.近年来,业界开展了大量研究探索中药通过调控NOD样受体热蛋白结构域相关蛋白3(NLRP3)焦亡通路治疗UC的作用机制,结果表明NLRP3焦亡通路是中药治疗UC的关键靶通路.但目前尚缺乏关于中药抑制NLRP3焦亡通路进而治疗UC的全面系统的总结.该文以"细胞焦亡""NLRP3""溃疡性结肠炎"及"中药"等为关键词,检索和分析近年来该领域中英文文献,发现调控NLRP3焦亡通路的中药主要包括清热燥湿类、调和气血类、行气通腑类和健脾祛湿类,这可为科研人员更为全面认识中医药对UC中NLRP3焦亡通路的机制提供帮助,以期为UC的治疗及进一步的药物开发提供理论依据.
Objective:To explore the quality differences between steamed products and raw products of Citri Reticulatae Pericarpium(CRP).Method:The color of steamed products and raw products of CRP was determined from the perspective of appearance by electronic eye technique,and the quality differences between them was objectively characterized by the luminous value(L * ),yellow-blue value(b * ),red-green value(a * ) and total chromatic value(E ab * ).Based on this,ultra-high performance liquid chromatography(UPLC) was used to establish a fingerprint evaluation method with the mobile phase of acetonitrile(A)-0.1%formic acid aqueous solution(B) for gradient elution(0-5 min,5%A;5-30 min,5%-20%A;30-60 min,20%-52%A),detection wavelength at 270 nm,flow rate of 0.3 m L·min -1 and column temperature of 30℃.The quality differences between steamed products and raw products of CRP were compared from the perspective of chemical composition,and correlation analysis was used to reveal the correlation between the difference in appearance color and the difference in internal chemical composition.Result:After being steamed,L * ,b * and E ab * of CRP showed an overall decreasing trend,indicating that the color of the steamed products darkened and deepened from yellow to blue but still tended to be yellow,while a * showed an overall increasing trend,indicating that the color of the steamed products tended to red.A total of 24 peaks were identified in the fingerprint profiles of raw products and steamed products of CRP,and 13 of the main peaks were identified.The precision,stability and repeatability studies showed that compared with the reference peak (peak 14,hesperidin),the relative standard deviations(RSDs) of the relative peak area and relative retention time of the remaining peaks were<3.0%.The results of chemometric statistical analysis showed that there were some differences between raw products and steamed products of CRP,and 7 main differential components were identified,among which 5-hydroxymaltol(peak 1) and 5-hydroxymethylfurfural(peak 2) were the characteristic components of steamed products.The correlation analysis results showed that,in addition to the above two characteristic components,four components of peak 4,peak 10 (vicenin-2),peak 23 (tangeretin) and peak 24 (5-demethylnobiletin) also correlated significantly with the color change (E ab * ) of the samples (P<0.05,P<0.01).Conclusion:Before and after steaming,not only the chemical composition changes,but also the color.Comparing the characteristic peaks of chemical composition difference and color difference before and after steaming of CRP,it is found that5-hydroxymaltol,5-hydroxymethylfurfural and peak 4 are common characteristic difference components,which can provide a reference for establishing the characteristic quality control method of steamed products,and quickly evaluating the quality difference between raw products and steamed products of CRP.
目的:观察葛花、枳椇子及其配伍对急性酒精性肝病的改善作用,为临床用药提供科学依据,并为开展其他酒精性相关疾病的研究提供思路和借鉴方法:采用一次性灌胃给予56%(V/V)红星二锅头酒(0.012 mL·g -1 )建立小鼠急性酒精性肝损伤模型,120只雄性ICR小鼠按体重随机分成空白组、模型组、水飞蓟宾组、葛花组、枳椇子组、葛花枳椇子配伍Ⅰ(配伍比例为1:1)组、葛花枳椇子配伍Ⅱ(配伍比例为1:2)组、葛花枳椇子配伍Ⅲ(配伍比例为2:1)组,每组15只。各给药组按0.01 mL· g -1 预防性灌胃相应药物3 d,除空白组外,其余各组小鼠按0.012 mL·g -1 分别灌胃给予二锅头酒,于酒后12 h处死小鼠,并观察药物对小鼠肝功能、抗氧化应激能力的影响;苏木素-伊红(HE)染色观察肝脏病理变化;蛋白免疫印迹法(Western blot)检测各组小鼠Kelch样ECH相关蛋白1(Keap1)-核转录因子E2相关因子2(Nrf2)-抗氧化响应元件(ARE)信号通路相关蛋白表达;实时荧光定量聚合酶链式反应(Real-time PCR)检测相关基因表达。结果:与正常组比较,模型组小鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)水平,肝组织中丙二醛(MDA)、活性氧(ROS)含量显著升高(P<0.01);谷胱甘肽(GSH)、超氧化物歧化酶(SOD)活性显著性降低(P<0.01)。与模型组比较,葛花-枳椇子(2:1)组小鼠ALT、AST和ALP水平显著减低(P<0.01),肝脏组织中MDA、ROS水平均显著减低(P<0.01),GSH、SOD水平均显著升高(P<0.01);肝脏脂肪变损伤均减轻,显著上调Nrf2 mRNA及蛋白表达(P<0.01),显著下调Keap1 mRNA及蛋白表达(P<0.01)。结论:葛花、枳椇子及其配伍组合对小鼠急性酒精性肝损伤有一定的预防作用,其机制可能与调控肝脏内Keap1/Nrf2/ARE信号通路,恢复并上调由乙醇所破坏的肝脏氧化平衡有关,从而有效遏制酒精性肝病的发展。
目的:探究柚皮苷对酒精诱导的急性肝损伤小鼠的药效学作用,为柚皮苷开发为解酒保肝药物提供数据支撑。方法:根据体质量将60只Balb/c小鼠随机分为对照组,模型组,柚皮苷低、高剂量组(25、50 mg·kg -1 ),海王金樽片阳性对照组(2 g·kg -1 )以及纳洛酮阳性对照组(2 mg·kg -1 )。各组小鼠灌胃或腹腔注射相应药物,对照组与模型组灌胃等体积0.5%羧甲基纤维素钠,每天给药1次,连续14 d。除对照组外,其他组在给药同时连续灌胃给予56°红星二锅头(13 mL·kg -1 )14 d诱导酒精性肝损伤模型。末次给药前1 d禁食不禁水12 h,末次灌胃白酒后2 h后摘眼球取血,解剖取得肝脏并称重。全自动生化仪检测谷丙转氨酶(ALT)和谷草转氨酶(AST)的表达水平;HE染色检测比较小鼠肝脏组织病理变化;TUNEL/DAB双染法观察阳性细胞数的比例判断细胞凋亡情况;蛋白免疫印迹法检测凋亡相关蛋白Bcl-2、Bax和Cyto C的表达。结果:与对照组比较,模型组小鼠肝体比显著增加(P<0.01),血清ALT和AST的表达显著增加(P<0.01),肝细胞胞浆显著疏松、水肿,脂肪变性较严重,有明显的出血现象,肝脏细胞凋亡增加,Bal-2表达水平与Bax表达水平比值降低(P<0.01),促凋亡蛋白Cyto C水平增加(P<0.01)。与模型组相比,柚皮苷低、高剂量组能显著降低肝体比(P<0.05,P<0.01),柚皮苷高剂量组能降低小鼠血清中ALT、AST活性(P<0.01),肝细胞脂肪变性显著减轻,肝细胞水肿消失,出血得到改善;肝细胞TUNEL阳性率显著降低;柚皮苷高低剂量均能显著降低Bal-2/Bax水平(P<0.05, P<0.01),提升了Cyto C水平(P<0.05)。结论:柚皮苷通过调节血清中ALT和AST的表达水平、减少肝脏脂肪病变和肝细胞凋亡,改善酒精引起的急性肝损伤。
目的:探讨启膈散(QGS)对食管癌细胞TE-1迁移和侵袭能力的影响机制.方法:利用基因芯片技术筛选正常组和启膈散组差异表达基因,分析差异基因的本体功能和信号通路.噻唑蓝(MTT)比色法检测QGS对TE-1细胞活性的影响.后续验证实验分为空白组、转化生长因子-β1(TGF-β1)组、TGF-β1+QGS组、TGF-β1+SB431542组.显微镜观察各实验组细胞形态,细胞划痕实验检测各组细胞的迁移和侵袭能力,实时荧光定量聚合酶链式反应(Real-time PCR)检测各组细胞E-钙黏蛋白(E-Cadherin)、波形纤维蛋白(Vimentin)、果蝇母本抗生存因子2(Smad2)和果蝇母本抗生存因子7(Smad7)mRNA的表达水平.蛋白免疫印迹法(Western blot)检测各组细胞E-Cadherin、Vimentin、p-Smad2/3、Smad2/3和Smad7蛋白的表达.结果:QGS组与空白组之间有1 487个差异基因,其中1 080个下调,407个上调,下调基因占差异基因的72.63%.下调基因涉及的主要生物学过程有细胞骨架蛋白结合、ATP结合、腺苷酸核苷酸结合、腺苷酸核糖核苷酸结合等,涉及的京都基因与基因组百科全书(KEGG)通路主要包括TGF-β信号通路、细胞周期、细胞外基质-受体相互作用蛋白、肿瘤中的通路、卵母细胞减数分裂等;上调基因主要参与RNA结合、DNA结合、转录调节子活性、转录激活子活性、核苷酸结合等生物学过程,涉及的KEGG通路主要包括丝裂原活化蛋白激酶(MAPK)信号通路、膀胱癌、肾细胞癌、癌中通路、p53信号通路等.与空白组比较,QGS(20、30、40、60、80 mg·L-1)干预TE-1细胞12、24、36、48、60h后,细胞活性抑制率明显增加,差异有统计学意义(P<0.05),抑制率呈时间和浓度依赖性.与空白组比较,TGF-β1组细胞变长,呈成纤维细胞表型.与TGF-β1组细胞比较,TGF-β1+QGS组细胞变短,形态恢复正常,呈上皮细胞表型;TGF-β1+SB431542组细胞形态与TGF-β1+QGS组相似.与空白组比较,TGF-β1组细胞的迁移和侵袭能力增强,差异有统计学意义(P<0.05).与TGF-β1组比较,TGF-β1+QGS组和TGF-β1+SB431542组细胞迁移和侵袭能力受到抑制而减弱,差异有统计学意义(P<0.05).但TGF-β1+QGS组和TGF-β1+SB431542组之间的迁移和侵袭能力差异无统计学意义.与空白组比较,TGF-β1组Vimentin和Smad2 mRNA的表达水平升高(P<0.05),E-Cadherin和Smad7 mRNA表达水平降低,差异有统计学意义(P<0.05).与TGF-β1组比较,TGF-β1+QGS组和TGF-β1+SB431542组的Vimentin和Smad2 mRNA表达水平降低,差异有统计学意义(P<0.05),E-Cadherin和Smad7 mRNA的表达水平升高(P<0.05).与空白组比较,TGF-β1组Vimentin、p-Smad2/3和Smad2/3的蛋白表达水平升高,差异有统计学意义(P<0.05),E-Cadherin和Smad7蛋白表达水平降低,差异有统计学意义(P<0.05).与TGF-β1组比较,TGF-β1+QGS组和TGF-β1+SB431542组的Vimentin、p-Smad2/3和Smad2/3蛋白表达水平降低,差异有统计学意义(P<0.05),E-Cadherin和Smad7蛋白表达水平升高,差异有统计学意义(P<0.05).结论:QGS乙酸乙酯提取物通过TGF-β1途径抑制TE-1细胞的上皮-间质转化过程,减少TE-1细胞的迁移和侵袭.
经典名方复方制剂开发是最近几年研究的热点,承载着政府、学术界和产业界的殷切盼望。在其研发过程中,反映出很多中医药行业的相关问题,值得学术界深思。本文基于目前经典名方开发现状,梳理关键问题并进行深入剖析,结果表明存在三方面因素影响其发展应予以重视。一是中医药基础研究薄弱,影响了其健康发展;二是对经典名方复方制剂开发的理解不够深入,相关政策需要更加合理;三是对经典名方开发的期望过高,影响了复方制剂研发进程。希望中医药行业能以此为契机,面对问题,提出解决方案,形成新的突破,推动中医药事业发展和进步。
功能化脂质体可以改善药物的体内过程进而实现药物的高效递送,主要表现为增强药物吸收、改变药物分布使其富集于靶标处、降低药物的消除以延长作用时间等特点,是目前纳米药物研究的热点方向之一,具有广阔的应用前景。查询中国国家药品监督管理局(NMPA)、美国食品药品监督管理局(FDA)及欧洲药品管理局(EMA)公布的药品信息发现目前上市的脂质体药物较少,且国内品种以仿制药为主,除聚乙二醇化脂质体外,没有其他功能化脂质体获批上市。由此可见功能化脂质体的临床转化率相对于发表的科研论文及专利处于较低水平。基于此,笔者查阅了近年来国内外功能化脂质体的相关研究案例,总结了功能化脂质体的概念和类别,围绕体内命运探讨了其在药物递送中的特点以及应用优势,分析了其临床转化率低主要有初期研究缺乏临床思维、功能性材料的有效性和安全性问题、体内外评价方法欠佳及放大生产困难等方面的原因,同时提出了引入临床多功能概念、加强各学科间交叉渗透以提高研究初期实验设计的合理性,着重考察功能性材料修饰密度及材料间相互作用、开发更为准确安全的脂质体体内外示踪技术、多角度多场景综合评价功能化脂质体递药性能以及进行以低成本和简便性为导向的处方组成及制备工艺优化等可能的应对策略,以期为功能化脂质体及其他载体类纳米药物的研发提供参考。
目的:通过观察萆薢分清丸对高尿酸(HUA)模型大鼠肾脏尿酸盐转运蛋白及mRNA水平的影响,探讨该方对高尿酸血症大鼠的干预作用机制。方法:60只雄性SD大鼠随机为正常组、模型组、别嘌醇组(0.03 g·kg -1 )和萆薢分清丸低、中、高剂量组(0.8、1.6、3.2 g·kg -1 )。除正常组外,其余各组大鼠每天灌胃氧嗪酸钾1.5 g·kg -1 和腺嘌呤0.1 g·kg -1 以建立HUA模型,连续28 d,以血尿酸(SUA)水平升高为标准。造模成功后依据组别给予相应药物干预,1次/d,连续28 d。末次给药24 h后,采集大鼠尿液和血液,采用酶比色法测定尿尿酸(UUA)、血尿酸(SUA)、尿素氮(BUN)、血肌酐(SCR)水平;取大鼠双侧肾脏,称重,计算肾脏系数;苏木素-伊红(HE)染色法观察肾脏病理变化;免疫组化(IHC)检测肾脏组织中尿酸转运体1(URAT1)、葡萄糖转运体9(GLUT9)、有机阴离子转运体1(OAT1)、有机阴离子转运体3(OAT3)、ATP结合盒转运蛋白G2(ABCG2)蛋白表达水平;实时荧光定量聚合酶链式反应(Real-time PCR)法检测URAT1、GLUT9、OAT1、OAT3、ABCG2 mRNA水平。结果:与正常组比较,模型组大鼠肾脏系数显著增加(P<0.05);SUA、BUN和SCR水平显著升高(P<0.05),UUA水平显著降低(P<0.05);肾小管代偿性扩张,管内可见尿酸盐结晶和蛋白管型;肾脏组织中URAT1、GLUT9蛋白表达水平及mRNA水平显著升高(P<0.05),OAT1、OAT3和ABCG2蛋白表达水平及mRNA水平显著降低(P<0.05)。与模型组比较,各给药干预组大鼠肾脏系数显著减小(P<0.05);SUA、BUN和SCR水平显著降低(P<0.05),UUA水平显著升高(P<0.05);肾脏组织病变明显减轻,URAT1、GLUT9蛋白表达水平及mRNA水平显著降低(P<0.05),OAT1、OAT3和ABCG2蛋白表达水平及mRNA水平显著升高(P<0.05)。结论:萆薢分清丸可通过调节尿酸盐转运蛋白表达水平来实现其对高尿酸血症的干预作用。
目的:比较两个不同茎叶色当归品种‘岷归1号’与‘岷归2号’转录水平差异。方法:以两种颜色当归的新鲜叶片(带叶柄)和上端茎为材料,采用混合测序策略,应用全长转录组技术构建当归无参全长转录本文库,利用RNA-seq技术对两品种进行差异基因表达分析,再利用公共数据库对差异基因的生物学功能进行注释和精细分类,筛选调控当归茎叶色差异的主要候选基因。结果:当归转录本的测序结果良好,测序数据质量较高,当归全长转录本的34 528条序列在NR、京都基因与基因组百科全书(KEGG)、SwissProt及KOG数据库中分别注释到33 947、33 241、29,150和22 601条。对两品种当归差异表达基因(DEGs)进行精细分类,具有生物学功能和分子功能的705个DGEs可分为11类,主要富集在初级代谢(17.87%)、逆境响应(14.47%)以及次级代谢(11.49%)等功能上,与颜色有关的差异表达基因主要集中在类黄酮生物合成途径上。结论:两品种当归茎叶颜色差异的主要原因可能与调控类黄酮的生物合成基因的表达差异有关,可为后续进行功能验证,进一步明确与当归主要药效成分之间的联系奠定基础。
卵巢功能减退类疾病主要包括卵巢储备功能减退、早发性卵巢功能不全、卵巢早衰等,是因多种原因造成女性生育力下降的一类疾病。卵巢颗粒细胞线粒体功能障碍会干扰生殖细胞能量供应路径,影响卵泡发育和卵子质量。因此,线粒体稳态在此类疾病发病机制中的作用逐渐受到重视。中医认为此类疾病的病机本质是肾气不足、精血亏虚,因虚致瘀,据此确立补肾养血活血为根本治疗大法,善用补肾益精和养血活血药物为主组成的中药复方,可有效改善卵巢性激素分泌及排卵功能以提高女性生殖能力,其临床疗效确切且具有异病同治的独特优势。补肾养血活血类中药复方对“气血”的作用与线粒体功能具有密切联系,越来越多的研究对补肾养血活血中药复方调控线粒体稳态以发挥保护卵巢功能的相关作用机制进行了实验探索。基于此,这篇综述总结阐述了补肾益精与养血活血中药共用的补肾养血活血中药复方动态调控线粒体稳态以治疗卵巢功能减退类疾病的实验研究,探讨补肾养血活血中药复方通过改善线粒体功能、对抗线粒体氧化应激损伤和调节线粒体质量与数量方式多效应、多靶点调控卵巢细胞内线粒体稳态,促进卵泡发育,延缓卵巢功能衰老的相关机制研究进展,以期为深层次研究中医药提高女性生育力提供新的角度。
肺癌发病率和死亡率均位居世界癌症前列,约85%的肺癌为非小细胞肺癌(non-small cell lung cancer,NSCLC),大多数患者在确诊时已是晚期,5年生存率较低,严重危害人类生命和健康。中医药在恶性肿瘤综合治疗中具有重要作用,口服中成药作为中医药的重要组成部分,具有制剂稳定、口感温和、携带方便、有效成分确切等区别于汤剂的优点,已广泛用于NSCLC的辅助治疗,在临床应用中不管是联合化疗、靶向治疗、放射治疗,还是单用维持治疗均可发挥增效减毒的功效,使治疗有效率提高,治疗相关毒副反应减轻,进而延长患者生存时间,改善患者生活质量。口服中成药辅助治疗NSCLC的作用机制主要包括抑制肺癌细胞的增殖、侵袭与转移,促进肺癌细胞凋亡,抑制肿瘤新生血管生成,逆转多药耐药,调节机体免疫功能,体现了中医药通过多途径、多通路、多靶点发挥抗肿瘤作用的特点。目前临床上常用于治疗NSCLC的口服中成药包括金复康口服液、参一胶囊、平消胶囊、消癌平片、康莱特胶囊、复方斑蝥胶囊、回生口服液、养正消积胶囊、西黄丸、紫龙金片、华蟾素胶囊等,这些中成药治疗NSCLC的临床与基础研究均较多,但缺乏系统性整合与梳理,故该文对目前临床上常用的口服中成药辅助治疗NSCLC的作用机制及临床应用研究进展进行系统综述,以期为后续研究和临床治疗提供参考。
目的:建立杜仲叶药材中5种成分(桃叶珊瑚苷、京尼平苷酸、绿原酸、车叶草苷、芦丁)含量测定的一测多评法(QAMS),并验证其在杜仲叶药材含量测定中的可行性和适用性,为杜仲叶药材质量标准的制定提供科学依据。方法:采用高效液相色谱法(HPLC),Welch Boltimate? C 18 色谱柱(4.6 mm×100 mm,2.7 μm),以甲醇(A)-0.2%磷酸水溶液(B)为流动相进行梯度洗脱(0~8 min,3%A;8~10 min,3%~11%A;10~26 min,11%A;26~27 min,11%~25%A;27~60 min,25%~32%A),流速0.6 mL·min -1 ,柱温30 ℃,检测波长210 nm和254 nm。以绿原酸为内参物,建立与其他4个指标成分之间的相对校正因子(f s/i ),并分别采用QAMS和外标法(ESM)测定14批杜仲叶药材中5种成分的含量。结果:桃叶珊瑚苷、京尼平苷酸、车叶草苷和芦丁的f s/i 分别为3.13,1.45,2.64,0.56,在不同实验条件下重复性良好,相对标准偏差(RSD)在0.5%~4.9%。测得14批杜仲叶中桃叶珊瑚苷、京尼平苷酸、绿原酸、车叶草苷、芦丁的质量分数分别为1.340~28.975,0.252~36.086,10.016~27.443,1.396~8.646,0.533~1.766 mg·g -1 ,QAMS与ESM比较,结果无明显差异(RSD<5.0%)。结论:以绿原酸为内参物建立的QAMS可用于杜仲叶药材中5种成分的含量测定,该方法简便易行、结果准确。经综合评估,建议绿原酸(不低于1.5%),桃叶珊瑚苷(不低于1.0%)及京尼平苷酸(不低于1.0%)作为杜仲叶的质量控制标准,可较好地避免因2005—2020年版《中国药典》指标成分(绿原酸)专属性差和含量限度过低而带来的潜在质量风险。
目的:基于小鼠原代骨髓巨噬细胞(BMDM),建立补骨脂定诱导的炎症小体活化模型,探索补骨脂定联合刺甘草查尔酮免疫调控的作用效应。方法:联用脂多糖与补骨脂定激活炎症小体,使用脂多糖(LPS)刺激BMDM 4 h后,给予刺甘草查尔酮(40 μmol·L -1 )进行预保护,1 h后用补骨脂定(10、20、40 μmol·L -1 )刺激4 h,采用蛋白免疫印迹法(Western blot)检测同时检测细胞上清中剪切成熟的胱天蛋白酶-1 p20(Caspase-1 p20)、和细胞裂解液中Caspase-1前体(pro-Caspase-1)、白细胞介素-1β前体(pro-IL-1β)的蛋白表达。结果:Western blot分析显示,刺甘草查尔酮可显著抑制补骨脂定诱导的pro-Caspase-1剪切成熟;酶联免疫吸附测定法(ELISA)试剂盒检测结果表明,与空白组比较,不同浓度得补骨脂定组均可以显著增加IL-1β、TNF-α释放(P<0.05);与补骨脂定组比较,补骨脂定-刺甘草查尔酮组均可显著减少IL-1β、TNF-α释放(P<0.01),表明刺甘草查尔酮与补骨脂定配伍可抑制补骨脂定诱导的炎症小体过度激活。此外,机制研究表明,刺甘草查尔酮通抑制补骨脂定诱导的凋亡相关斑点样蛋白(ASC)寡聚从而抑制炎症小体的激活。结论:刺甘草查尔酮可显著抑制补骨脂定介导的过激的免疫炎症反应,从而达到配伍减毒的效应,本研究探索了补骨脂定-刺甘草查尔酮配伍减毒的效应,在一定程度上为临床安全用药提供依据。
目的:探讨白细胞介素-6(IL-6)/信号传导及转录激活因子3(STAT3)通路在湿热内蕴证溃疡性结肠炎(UC)辅助性T细胞17(Th17)/调节性T细胞(Treg)失衡中的作用及芍药汤的干预机制。方法:将60只SD大鼠随机分为空白组、模型组、西药对照组(0.42 g·kg -1 )、芍药汤低、中、高剂量组(11.1、22.2、44.4 g·kg -1 ),除空白组外,其他各组采用复合病因造模建立湿热内蕴证溃疡性结肠炎模型,各组分别给予生理盐水、美沙拉嗪组、芍药汤低、中、高剂量治疗14 d。末次给药24 h后处死大鼠提取脾脏、结肠组织,采用苏木素-伊红(HE)染色观察结肠组织病理学改变,免疫组化(IHC)法检测结肠组织白细胞介素-17(IL-17)、转化生长因子-β 1 (TGF-β 1 )水平;流式细胞术检测脾脏Th17/Treg细胞水平;蛋白免疫印迹法(Western blot)检测结肠组织IL-6、STAT3蛋白水平。结果:与空白组比较,模型组结肠出现充血、糜烂等病变,脾Treg细胞百分比显著降低(P<0.01),Th17细胞百分比显著升高(P<0.01),结肠组织IL-6、STAT3蛋白水平显著升高(P<0.01);与模型组比较,各药物组结肠损伤减轻,脾Treg细胞百分比显著升高(P<0.01),Th17细胞百分比显著降低(P<0.01),结肠组织中IL-6、STAT3蛋白水平显著降低(P<0.01)。结论:芍药汤通过抑制IL-6/STAT3通路调节Th17/Treg平衡,进而改善湿热内蕴证UC大鼠的病理损伤,影响其免疫功能。
从全球范围来看,中国是消化道疾病较为流行的国家,其中以消化道肿瘤为著,主要包括肝癌、胰腺癌、结直肠癌等.消化道肿瘤新发病例数与死亡例数均占全球癌症前10位,且肿瘤疾病发生率与死亡率呈逐年增长趋势,因此肿瘤的预防与治疗显得尤为重要.随着中药在医学界的推广应用及分子生物学和药理学的迅速发展,越来越多的中药潜在活性成分被提取出来并经研究证实,其以多靶点、多通路的原理有效地抑制肿瘤细胞,发挥中药抗肿瘤作用.华蟾素是源于中华蟾蜍的皮经提取分离得到的有效组分,临床上被制成多种剂型,并具有抗肿瘤、调节免疫、强心升压、镇痛、抗炎消肿等作用.现代临床多用于肝癌、肺癌、结直肠癌、胃癌等恶性肿瘤的治疗,改善中晚期患者的不良反应,提高患者生活质量及5年生存率.分子机制研究表明华蟾素可通过诱导细胞凋亡、调控细胞周期抑制细胞增殖、抑制血管生成、调节免疫应答、逆转多药耐药和放化疗增敏、抑制肿瘤炎症及侵袭转移等多种途径发挥疗效.该综述着重于强调近年来在国内外相关研究中对华蟾素抗消化道肿瘤疾病的临床应用与机制,为华蟾素抗肿瘤研究提供理论依据,推进华蟾素辅助或临床联合治疗手段,为药物的再次开发与研究应用提供参考条件.
Objective: Based on the supramolecular "imprinting template" theory, the autonomous action law of the component groups of Shentong Zhuyutang in the preparation process of medicinal materialsdecoction pieces-formulas was studied to clarify the quantitative transfer law of its quality attributes. Method: Ultra performance liquid chromatography(UPLC) fingerprint of Shentong Zhuyutang was established with mobile phase of 0.4% phosphoric acid aqueous solution(A)-acetonitrile(B) for gradient elution(0-2.5 min, 100%A; 2.5-6 min, 100%-96%A; 6-15 min, 96%-92%A; 15-25 min, 92%-88%A; 25-35 min, 88%-75%A; 35-50 min, 75%-65%A; 50-60 min, 65%-50%A; 60-65 min, 50%-30%A; 65-70 min, 100%A) and detection wavelength of 235 nm, and the total statistical moments, information entropy and primary feeding amount of fingerprint of medicinal materials, decoction pieces and benchmark samples were calculated. Dry extract rate of the benchmark samples, the transfer rates and the addition parameters of medicinal materials-decoction piecesformulas were calculated. Result: Similarities of the total statistical moments of UPLC fingerprint of 15 batches of medicinal materials and decoction pieces were>0.89, the relative standard deviations(RSDs) of information entropy of UPLC fingerprint of 12 medicinal materials and decoction pieces were<10%. RSDs of total first-order moment(MCRTT) and information entropy of Shentong Zhuyutang(medicinal materials) were 5.5% and 2.3%, while the RSDs of MCRTT and information entropy of Shentong Zhuyutang(decoction pieces) were 4.8% and 2.6%, respectively. The dry extract rate of 45 batches of Shentong Zhuyutang was 17.2%-20.2%. The transfer rate of medicinal materials to decoction pieces was within the range of data fluctuation, which was 70%-130% of the average value. The overall transfer rates of medicinal materials to decoction pieces and decoction pieces to benchmark samples were 101.8% and 83.0%, respectively. Conclusion: The quality properties of Shentong Zhuyutang benchmark samples can be studied by total statistical moment analysis and primary feeding amount analysis, which can confirm the supramolecular "imprinting template" theory to a certain extent.
Hyperlipidemia is a dyslipidemia caused by dyslipidemia of lipid metabolism, which can be divided into primary and secondary types. The current clinical diagnostic criteria are mainly changes in lipid levels, which are the inducers of high-risk cardiovascular diseases such as atherosclerosis, pancreatitis and coronary heart disease. As a key target in lipid metabolism, peroxisome proliferator-activated receptor α(PPARα) is involved in a variety of metabolic activities, including fatty acid degradation, synthesis, transport, storage, lipoprotein metabolism, etc. Activation of PPARα can maintain the balance of lipid metabolism through a variety of ways, which is an important way to treat hyperlipidemia. At present, chemical drugs such as statins and bettes are mainly used in the clinical treatment of hyperlipidemia. Although they can slow down the disease to a certain extent, there are many adverse reactions and drug resistance. By reviewing the literature in recent years, the author found that the activation of PPARα pathway by traditional Chinese medicine in the treatment of hyperlipidemia has significant effect and small adverse reactions. The lipid-lowering active ingredients include flavonoids, alkaloids, phenols, terpenoids and other compounds. These active components mainly affect the expression of downstream effectors through the activation of PPARα pathway, thereby inhibiting the synthesis of total cholesterol and promoting fatty acid oxidation, and play a role in the treatment of hyperlipidemia. In this paper, we systematically reviewed the structure types and mechanism of active components of traditional Chinese medicine that activate PPARα pathway, so as to provide guidance for the rational development and clinical application of lipid-lowering traditional Chinese medicine new drugs.