Asari Radix et Rhizoma is a common drug for relieving exterior syndrome in clinics,but its toxicity limits its use.In this study,the mechanism of hepatic damage of Asari Radix et Rhizoma was studied by network pharmacology and metabolomics.The hepatic damage-related dataset,namely GSE54257 was downloaded from the GEO database.The Limma package was used to analyze the differentially expressed genes in the dataset GSE54257.Toxic components and target genes of Asari Radix et Rhizoma were screened by TCMSP,ECTM,and TOXNET.The hepatic damage target genes of Asari Radix et Rhizoma were obtained by mapping with the differentially expressed gene of GSE54257,and a PPI network was constructed.GO and KEGG enrichment analysis of target genes were performed,and a"miRNA-target gene-signal pathway"network was drawn with upstream miRNA information.Thirty rats were divided into a blank group,a high-dose Asari Radix et Rhizoma group,and a low-dose Asari Radix et Rhizoma group,which were administered once a day.After continuous administration for 28 days,liver function indexes and liver pathological changes were detected.Five liver tissue samples were randomly collected from the blank group and high-dose Asari Radix et Rhizoma group,and small molecule metabolites were analyzed by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS).The orthogonal partial least squares-discriminant analysis(OPLS-DA)method was used to screen differential metabolites,and enrichment analysis,correlation analysis,and cluster analysis were conducted for differential metabolites.Finally,the MetaboAnalyst platform was used to conduct pathway enrichment analysis for differential metabolites.It was found that there were 14 toxic components in Asari Radix et Rhizoma,corresponding to 37 target genes,and 12 genes related to liver toxicity of Asari Radix et Rhizoma were obtained by mapping to differentially expressed genes of GSE54257.The animal test results showed that Asari Radix et Rhizoma could significantly increase the liver function index,reduce the activity of the free radical scavenging enzyme,change the liver oxidative stress level,and induce lipid peroxidation damage in rats.The results of untargeted metabolomics analysis showed that compared with the blank group,nine metabolites were up-regulated,and 16 metabolites were down-regulated in the liver tissue of the Asari Radix et Rhizoma group.These 25 metabolites had strong correlations and good clustering.Pathway enrichment analysis showed that these differential metabolites and the 12 hepatotoxic target genes of Asari Radix et Rhizoma were mainly involved in purine metabolism,as well as the biosynthesis and metabolism of valine,leucine,glycine,serine,and threonine.The study confirmed that the hepatica damage effect of Asari Radix et Rhizoma was the result of multi-component,multi-target,and multi-signaling pathways,and its mechanism may be related to inhibiting nucleotide synthesis and affecting protein metabolism.

胃溃疡是一类患病率高的脾胃病,具有多发、易患、反复、难愈等特点.目前临床上已有众多相关治疗药物,然多数仅有助于缓解症状,难以根本治愈.党参具有健脾益肺、生津养血的功效,药效偏缓且滋益,在治疗胃溃疡方面具有突出疗效,能够有效降低溃疡指数、调节胃肠动力、加速溃疡愈合.通过检索查阅CNKI、万方、Pubmed等数据库文献,综合论述党参药材、党参提取物及其药效成分治愈胃溃疡的作用机制,以期为进一步深入挖掘党参在脾胃方面的应用价值提供科学依据和科研思路.

复方甘草含片是在复方甘草片基础上的一次剂型改革,将甘草片改进为含片,使其成为味道适宜、质量稳定的新剂型,主要有镇咳、祛痰、消炎作用.通过实践研究发现,复方甘草含片镇咳祛痰的疗效强于复方甘草片.本文通过查阅分析相关文献,从药理作用、临床疗效、制备工艺、质量控制4个方面系统地阐述了复方甘草含片的研究进展及所取得的进步,为其在临床上合理应用进一步提供了依据.

目的:考察比较市售复方甘草含片与复方甘草片处方组分的稳定性.方法:按照2020版《中国药典》9001技术要求,观察影响因素及加速条件对复方甘草含片和复方甘草片处方组分稳定性的影响.结果:复方甘草含片和复方甘草片在高温、高湿条件下组分甘草酸和吗啡稳定,八角茴香油和樟脑有损失,在强光照射条件下组分甘草酸、吗啡、八角茴香油和樟脑均有损失,而八角茴香油和樟脑的损失率更高.结论:在高温、高湿及强光照射条件下复方甘草含片处方组分的损失率明显低于复方甘草片,将复方甘草片改进工艺制成复方甘草含片,其组分的稳定性明显提高,对复方甘草含片与复方甘草片的制备方法和药品储藏有一定的指导意义.

目的 观察党参多糖对大鼠溃疡性结肠炎的保护作用,并探讨其对结肠上皮NF-KB信号通路的影响.方法 50只雄性Wistar大鼠随机分为5组(每组10只),分别为正常组、模型组、柳氮磺胺嘧啶(SASP)阳性对照组(0.3g/kg)、党参多糖高剂量组(9g/kg)、党参多糖低剂量组(3 g/kg),采用三硝基苯磺酸(TNBS)/乙醇联合灌肠制作大鼠实验性溃疡性结肠炎(UC)模型.给药21 d后,观察大鼠疾病活动指数(DAI)、结肠黏膜损伤指数(CMDI)及结肠组织形态,生化法及ELISA法分别检测结肠组织中SOD(超氧化物歧化酶)活性、MDA(丙二醛)、白介素IL-6、IL-10和TNF-α(肿瘤坏死因子-α)水平,RT-PCR检测结肠组织中IL-6、IL-10、TNF-α mRNA表达,免疫组化法及Western blot法测定结肠组织中NF-κB蛋白表达.结果 党参多糖高低剂量组均能降低UC大鼠DAI评分、CMDI评分,改善结肠黏膜形态,降低结肠组织中MDA、IL-6、TNF-α水平,提高结肠组织中SOD活性和IL-10水平(P＜0.01),抑制IL-6、TNF-αmRNA 表达,促进IL-10 mRNA 表达(P＜0.01),抑制 NF-κB 蛋白表达(P＜0.01).结论 党参多糖具有保护大鼠溃疡性结肠炎的作用,其机制可能与抗脂质过氧化、抑制NF-KB信号通路减少炎症因子释放有关.

Objective: To study the protective effects and mechanisms of total saponins of Codonopsis (TSC) on ulcerative colitis in rats. Methods: Fifty male Wistar rats were randomly divided into 5 groups: control group, model group, salazosulfadiazine (SASP) positive control group (0.3 g/kg), TSC high- and low-dose experimental groups(1.2, 0.4 g/kg). UC rat model was established by trinitrobenzene sulfonic acid (TNBS)/ ethanol enema. After administration for 21 days, the rats' symptoms and signs, disease activity index (DAI), colonic mucosal injury index (CMDI) and colonic tissue morphology were observed. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor (TNF-α) in colon tissues were determined. Protein expression of nuclear nuclear transcription factor-κB (NF-κB) in colon tissues was detected. Finally, the effect of TCS therapy was evaluated. Results: Compared with the control group, the DAI and CMDI scores of the rats in the model group were increased significantly, meanwhile the colonic mucosa was seriously damaged, indicating that the model was successful. Compared with the model group, the TSC high and low dose groups could significantly reduce the DAI and CMDI score (P＜0.05) and improve the colonic mucosa form. TSC also could increase the SOD activity and decrease MDA content in colon tissues(P＜0.05), while inhibit the levels of IL-6 and TNF-α mRNA in the colon tissues and promote the expression of IL-10 mRNA (P＜0.01). At the same time, TSC reduced the expressions of NF-κB protein in the colon (P＜0.01). The TSC high-dose group was superior to the low-dose group (P＜0.05). Conclusion: TSC has significant protective effects on ulcerative colonic mucosal damage in UC rats, and there is a dose-dependent relationship; its mechanism may be related to anti-lipid peroxidation and inhibiting the NF-κB signaling pathway to regulate the release of inflammatory factors.

研究党参水煎液对大鼠实验性溃疡性结肠炎(UC)的保护作用并探讨其抗炎作用机制.将40只大鼠随机分为正常组、模型组、阳性对照组(柳氮磺胺嘧啶,SASP;0.3 g/kg)和党参水煎液组(18 g/kg),用三硝基苯磺酸(TNBS)/乙醇联合灌肠建立大鼠UC模型,连续给药21 d,观察大鼠一般情况,进行疾病活动指数(DAI)和结肠黏膜损伤指数(CMDI)评分;H.E染色观察结肠组织形态;生化法检测结肠中超氧化物歧化酶(SOD)和丙二醛(MDA)含量;RT-PCR法检测结肠组织白介素-6(IL-6)、白介素-10(IL-10)及肿瘤坏死因子(TNF-α)的mRNA表达;免疫组化法检测结肠组织中NF-κB的蛋白表达.结果 表明,党参水煎液能显著降低UC大鼠DAI评分、CMDI评分(P＜0.01);改善结肠黏膜形态;升高结肠组织中SOD活力,降低MDA含量(P＜0.01);抑制结肠组织中IL-6、TNF-α mRNA水平,促进IL-10 mRNA表达(P＜0.01);同时降低结肠中NF-κB的蛋白表达(P＜0.01).提示党参水煎液对大鼠溃疡性结肠炎具有保护作用,其抗炎机制可能与抗脂质过氧化,抑制NF-κB的表达而减少促炎因子的释放有关.

查阅近年来关于植物类、动物类、矿物类中药引发肝损伤的相关文献,总结可导致肝损伤的中药及其作用机制,为中药致肝损伤的预防提供参考,也为中药的合理应用提供理论支持.

研究湿生扁蕾乙酸乙酯提取物(GEE)对乙醇诱导人正常肝细胞(L02)氧化损伤的保护作用及其机制.用400 μmol/L乙醇诱导L02细胞建立体外细胞氧化损伤模型,加入GEE 25 μg/mL、50 μg/mL、100μg/mL作用24h,采用MTT法检测细胞存活率;检测细胞培养上清液中谷丙转氨酶(ALT)、谷草转氨酶(AST)、细胞内超氧化物歧化酶(SOD)和丙二醛(MDA)含量的变化;DCFH-DA探针染色流式细胞仪检测细胞内ROS水平;DTNB-GR动力学循环法检测胞内还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)的含量变化.结果 表明,400μg/mL乙醇诱导L02细胞24h可建立肝细胞氧化损伤模型.GEE在25～100 μg/mL对L02细胞无损伤.与模型组比较,GEE中剂量、高剂量组能显著提高L02细胞存活率(P＜0.001);降低细胞上清液中ALT、AST含量(P＜0.001);使细胞内SOD活力显著提高(P＜0.001);MDA含量明显降低(P＜0.001);同时使细胞内ROS水平降低(P＜o.01)、GSH/GSSG比值提高(P＜0.001).提示GEE对乙醇诱导的L02细胞损伤具有保护作用,其机制可能与其减轻氧化应激反应有关.

查阅相关文献,从抗肿瘤,止泻,保肝、利胆,抑菌,抗结肠纤维化,抗炎、镇痛,抗氧化及其他等8个方面对藏药湿生扁蕾的药理作用进行概述,为其临床应用及后续的进一步研究开发提供理论依据.

目的 探究湿生扁蕾不同提取物抗氧化活性与其中所含当药黄素、当药醇苷、木犀草素的相关性.方法 采用高效液相色谱(HPLC)法同时检测湿生扁蕾不同提取物中当药黄素、当药醇苷、木犀草素含量;通过DPPH·清除实验和ABTS+自由基清除实验两种体系,评价各提取物的抗氧化活性;采用Pearson相关性分析和灰色关联分析法,研究湿生扁蕾不同提取物中当药黄素、当药醇苷、木犀草素含量与抗氧化活性之间的相关性.结果 湿生扁蕾乙酸乙酯提取物中当药黄素含量最高,为68.19 mg·g-1;95％乙醇提取物中当药醇苷含量最高,为21.03 mg·g-1;正丁醇提取物中木犀草素含量最高,为19.38 mg·g-1.95％乙醇提取物对DPPH·清除能力最强,IC50值为0.124 mg·mL-1;正丁醇提取物对ABTS+自由基清除能力最强,IC50值为0.036 mg·mL-1.Pearson相关性分析发现,与木犀草素相比,当药醇苷含量与DPPH·清除能力、ABTS+清除能力相关性较好,相关系数R2分别为0.994、0.823;而木犀草素相关系数分别为0.875、0.746.然而,灰色关联分析结果 表明木犀草素含量和当药醇苷含量与DPPH·清除能力、ABTS+清除能力均有较强的关联度.结论 湿生扁蕾提取物中的当药醇苷和木犀草素与其体外抗氧化性有较好的相关性,当药醇苷含量可作为评价湿生扁蕾提取物体外抗氧化性的主要指标性成分.

目的 探讨当归对阴虚哮喘小鼠气道杯状细胞增生及JAK1/STAT6信号通路的影响.方法 采用卵清白蛋白与甲状腺复制阴虚哮喘动物模型,观测当归对阴虚哮喘小鼠肺通气功能、哮喘气道杯状细胞增生、肺组织中Muc5ac、IL-13、IL-4含量以及JAK1与STAT6表达水平的影响.结果 当归可明显缓解阴虚哮喘小鼠呼吸频率、潮气量及增强呼气间歇的异常变化,改善肺功能,降低肺指数及肺组织湿干重比值,抑制气道杯状细胞增生,降低肺组织中Muc5ac、IL-13及IL-4含量,抑制肺组织JAK1及STAT6蛋白的表达(P＜0.05或P＜0.01).结论 当归具有明显缓解气道杯状细胞增生及Muc5ac高表达而平喘的作用,抑制JAK1/STAT6信号通路是其改善哮喘气道黏液分泌失衡的作用机制之一.

Keap1-Nrf2-ARE信号通路是细胞防御氧化应激损伤的最重要机制之一。许多具有解毒、抗氧化防御功能的蛋白质,其转录调控都依赖于Nrf2信号通路的激活。研究表明,Nrf2信号通路已成为氧化应激相关疾病（神经退行性疾病、癌症、心血管系统疾病、代谢和炎症等疾病）预防和治疗的靶点。因此,Nrf2信号通路的激活剂在多种氧化应激诱发的疾病方面都表现出良好的预防及治疗作用,发现及研究Nrf2信号通路的激活剂已越来越受到研究者们的重视。该文概述了Keap1-Nrf2-ARE通路的作用机制,并阐述了Keap1-Nrf2-ARE信号通路小分子激活剂的研究进展。

熏倒牛为牻牛儿苗科熏倒牛属植物,是一种传统藏药,其主要分布在我国甘肃、青海、宁夏六盘山西坡、四川西北部(诺尔盖)等地区.近年来对熏倒牛活性成分的研究证明其具有抑菌、抗炎镇痛、镇静解痉、抗氧化、降血糖降血压等作用.本文对熏倒牛的研究进行分析和总结,从化学成分、药理作用、毒理学、质量标准等方面进行了综述,为其后续的进一步开发提供科学依据.

目的 探讨作业治疗结合经皮神经电刺激治疗复杂区域性疼痛综合征1型患者的临床疗效.方法 选取2015年1月至2018年6月附属医院康复科收治的复杂区域性疼痛综合征1型患者30例,并随机分为对照组15例和实验组15例.对照组给予经皮神经电刺激(TENS)治疗,实验组给予作业治疗结合经皮神经电刺激(TENS),均为每天40分钟,每周5天,共4周.并在治疗前后使用视觉模拟评分量表(VAS)、手部水肿8字测量法、改良Barthel指数进行评价.结果 针对两组患者治疗前后的VAS评分、手部水肿维度进行比较,差异有统计学意义(P<0.05),患者的疼痛及水肿有明显改善.结论 作业治疗结合经皮神经电刺激治疗对患者的疼痛缓解、消肿、日常活动参与能力的促进有良好的效果.

目的:探讨湿生扁蕾(口山)酮对溃疡性结肠炎(UC)肠纤维化大鼠肠上皮细胞中ATG16L1、LC3表达的影响.方法:大鼠UC肠纤维化模型由TNBS诱导,后经湿生扁蕾(口山)酮干预,以柳氮磺胺吡啶为阳性对照.结肠组织HE染色,进行组织病理学观察.免疫组化法与蛋白免疫印迹法结合测定各组ATG16L1、LC3蛋白表达.结果:与模型组比较,湿生扁蕾(口山)酮各剂量组及柳氮磺胺吡啶组结肠组织中ATG16L1、LC3蛋白表达较模型组显著降低(P＜0.05).结论:湿生扁蕾(口山)酮可抑制UC肠纤维化模型大鼠肠上皮细胞ATG16L1、LC3蛋白的表达,其治疗肠纤维化的作用机制可能与其保护结肠黏膜上皮屏障系统有关.

目的:探究湿生扁蕾乙酸乙酯部位对结肠癌微环境中人骨髓间充质干细胞(human mesenchymal stem cells,HMSCs)恶性增殖及表面标志分子CD34、CD90表达的影响.方法:通过MTT法筛选湿生扁蕾乙酸乙酯部位作用于SW480细胞和HMSCs的最佳给药剂量.建立SW480和HMSCs细胞Transwell非接触共培养模型,将试验分为正常对照组、肿瘤细胞对照组、共培养组和湿生扁蕾给药组,分别采用细胞计数试验、流式细胞术FCM观察各组细胞的增殖、周期及HMSCs表面标志分子CD34和CD90的表达情况.结果:湿生扁蕾乙酸乙酯部位最佳给药剂量为200μg/ml,100μl.与正常对照组相比,共培养组HMSCs增殖能力增强,G1期细胞比例明显降低,S期和G2/M期细胞比例明显升高,且HMSCs表面标志分子CD34阳性表达率升高,CD90阳性表达率降低.与共培养组相比,湿生扁蕾给药组HMSCs增殖能力降低,G1期细胞比例明显升高,S期和G2/M期细胞比例明显降低,且HMSCs表面标志分子CD34阳性表达率降低,CD90阳性表达率升高.结论:结肠癌微环境中HMSCs增殖能力增强,且HMSCs表面标志分子阳性表达率发生显著改变,提示HMSCs发生恶性增殖,且湿生扁蕾乙酸乙酯部位可抑制结肠癌微环境中HMSCs的恶性转变.

Objective To investigate the effect of Gentianopsis paludosa on expressions of transforming growth factor-β (TGF-β) and structure in ulcerative colitis (UC)fibrosis rats.Methods The SD rats were randomly divided into five groups:normal,model,positive control and experimental-L,experimental-M and experimental-H groups,12 rats in each group.Fibrosis model rats was induced with trinitrobenzene sulphonic acid except for rats in normal group.Rats in experimental groups were administered with 50％ ethanol solution and the corresponding drugs 5.6,2.8,1.4 g · kg-1,respectively;rats in positive control group was administered sulfasalazine pyridine suspension 200 mg · kg-1;rats in normal,model groups were administered equivalent 0.9％ NaCl,by gavage for 2 weeks.At the end of the treatment,cell morphology was analyzed by hematoxylin eosin (HE).The fibrosis was analyzed by Masson.The expression of TGF-β was analyzed by immunohistochemistry.Results Comparison between positive control group and experimental-M group,the fibrosis of UC was obviously mitigated,TGF-β expression of UC fibrosis rats was significantly decreased.Conclusion The inhibitory effect on fibrosis was observed in experimental groups,which may be related to the expression of TGF-β.

OBJECTIVE To study the therapeutic effects of Yuyin Ruangan granule (YRG) on liver fibrosis and Yin-deficiency syndrome in rats.METHODS Replicating a model of liver fibrosis through multiple factor,and researching preventive and therapeutic effect of YRG on liver fibrosis rats by measuring indexes of hepatic fibrosis(ALT,AST,liver index,liver histopathology,hydroxyproline and collagen protein) and Yin-deficiency indexes (the quantity of eating and drinking water,locomotor activity,body weight,cAMP and cGMP).RESULTS YRG(1.08-4.32 g.kg-1) could decrease ALT and AST in serum of liver fibrosis rats,reduce hepatic index and content of hydroxyproline and collagen protein,and remit liver fibrotic pathological changes.Meanwhile YRG could reduce water intake,put on weight,decrease frequency of activity and standing,and lower cAMP and cAMP/cGMP.CONCLUSION Rat model with hepatic fibrosis replicated by multi-factor has certain Yin-deficiency syndrome,and YRG has some preventive and therapeutic effects on liver fibrosis and its Yin-deficiency syndrome.

OBJECTIVESTo observe the preventive and therapeutic action of Yuyin Ruangan Granule (YRG, Traditional Chinese Medicine) in hepatic fibrosis rats model and its effect on transforming growth factor-β1 (TGF-β1) expression.METHODSThe Wistar rats were randomly divided into 6 group (n=10), and the model of hepatic fibrosis rats was established by subcutaneous injected with carbon tetrachloride (CCL4), fed on high-fat diet and 20% ethanol for 6 weeks, to survey the effect and mechanism of YRG preventing hypatic fibrosis by detecting liver function (the activity of alanine aminotransferase(ALT), aspartate aminotransferase(AST), etc.) of liver fibrosis rats, liver fibrosis indicators (hyaluronic acid, Ⅲ procollagen, type IV collagen, laminin and hepatic pathology, etc.), and TGF-β1 expression in liver tissue after 6 weeks treated with YRG through intragastric administration (q. d.).RESULTSAt the 7th week, fibrotic lesions appears distinctly in liver tissue of model group compared with control group (P<0.01), YRG of 6.2~28.8 g/kg could significantly decrease hepatic index, ALT and AST activities, content of hyaluronic acid(HA), Ⅲ procollagen (PCⅢ), type Ⅳ collagen(C-Ⅳ), laminin (LN) in serum, relieve liver fibrosis pathological changes and inhibit TGF-β1 expression in fibrotic liver tissue (P<0.05, P<0.01).CONCLUSIONSYRG has significantly preventive effects on liver fibrosis rats model, and it may be one of its mechanisms to inhibit expression of TGF-β1.