基于网络药理学探讨白花蛇舌草-半枝莲抗肝细胞癌的作用机制

[目的]基于网络药理学探讨白花蛇舌草-半枝莲药对治疗肝细胞癌的潜在靶点及作用机制。[方法]利用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)检索白花蛇舌草和半枝莲活性成分,导入Drugbank数据库进行蛋白靶点匹配,使用GeneCards数据库、人类在线孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库、治疗目标数据库(Therapeutic Target Database,TTD)、Drugbank、肝细胞癌肿瘤数据库(Oncogenomic Database of Hepatocellular Carcinoma,OncoDB.HCC)和Liverome数据库等获取肝细胞癌相关靶点,运用Cytoscape构建“药物-活性成分-靶点”网络,String数据库构建蛋白相互作用(protein-protein interaction,PPI)网络,并通过网络拓扑分析筛选关键成分及核心靶点,最后利用R语言及Cluego对预测得到的核心靶点进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。[结果]白花蛇舌草-半枝莲药治疗肝细胞癌的潜在靶点 89个,通过网络拓扑分析筛选得到6个核心靶点、5种关键成分。GO功能富集分析显示,白花蛇舌草-半枝莲药对主要参与细胞增殖、细胞凋亡、炎症反应和血管生成等生物学途径。KEGG通路富集分析显示,p53抑癌基因通路、磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol-3-kinase/protein kinase B,PI3K-Akt)通路、缺氧诱导因子-1(hypoxia inducible factor-1,HIF-1)通路、核因子-κB(nuclear factor-κB,NF-κB)通路、血管内皮生长因子(vascular endothelial growth factor,VEGF)通路等是其关键信号通路。[结论]白花蛇舌草-半枝莲药对中有效成分主要是槲皮素、木犀草素、β-谷甾醇等,通过调节p53、PI3K-Akt、HIF-1、NF-κB和VEGF等信号通路抑制肝癌细胞增殖,并促进细胞凋亡,减少炎症反应,抑制血管生成,从而实现对肝细胞癌的治疗作用。     

基于网络药理学探讨红曲-山楂治疗NASH的作用机制及关于NF-κB信号通路的机制验证

[目的] 基于网络药理学预测红曲-山楂治疗非酒精性脂肪性肝炎(non-alcoholic steatohepatitis，NASH)的潜在分子机制，并采用蛋氨酸-胆碱缺乏NASH模型对核心信号通路之一的核因子-κB(nuclear factor-κB，NF-κB)信号通路进行实验验证。[方法] 通过中医药数据和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)、PubChem、Swiss Target Prediction等数据库获取红曲、山楂的有效成分及靶点，运用基因组注释数据平台(Genome Annotation Database Platform，GeneCard)、在线人类孟德尔遗传(Online Mendelian Inheritance in Man，OMIM)等数据库获取NASH的疾病靶点，结合 Cytoscape软件构建药物-成分-靶点拓扑图；取交集靶点并筛选核心共靶基因，应用 STRING数据库构建蛋白互作(protein-protein interaction，PPI)网络；应用Metascape进行基因本体(gene ontology，GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes，KEGG)富集分析。建立大鼠NASH模型，通过一般情况、生化检验、苏木素-伊红(hematoxylin-eosin，HE)染色、Masson染色、聚合酶链式反应(polymerase chain reaction，PCR)、免疫印迹等方式验证网络药理学分析结果。[结果] 通过网络药理学共筛选出18个活性成分，54个关键靶点，GO分析结果涉及炎症、代谢、自噬、肿瘤等，KEGG结果涉及NF-κB等经典信号通路。动物实验结果显示，红曲-山楂干预可显著改善NASH小鼠脂肪变性及炎症改变情况，降低组织中白细胞介素-1β(interleukin-1β，IL-1β)、白细胞介素-6(interleukin-6，IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)等炎症因子水平，降低核因子-κB(nuclear factor-κB，NF-κB)p65、NF-κB p50、NF-κB抑制蛋白-α(inhibitor of NF-κB-α，IκB-α)基因水平，下调NF-κB p65、NF-κB p50、磷酸化NF-κB-p65(phospho-NF-κB-p65，p-NF-κB p65)蛋白的表达。[结论] 红曲-山楂可能通过调控NF-κB信号通路，改善NASH模型小鼠的症状，本研究结果可为红曲-山楂的临床应用提供依据。     

基于网络药理学和分子对接技术探讨白术治疗溃疡性结肠炎的潜在分子机制

[目的]通过网络药理学方法探讨白术治疗溃疡性结肠炎(ulcerative colitis,UC)的潜在分子生物学机制。[方法]从中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database,TCMSP)等数据库及Pubmed文献数据库中检索并获取与白术相关的活性成分及潜在作用靶点,构建白术活性成分-潜在靶点网络;通过DisGeNET、药物靶标数据库(Therapeutic Target Database,TTD)、GeneCards数据库筛选与UC相关的靶点,利用Venny 2.1软件绘制韦恩图并获取药物及疾病共有靶点;通过Cytoscape软件BisoGenet插件分析得到蛋白互作网络及核心靶点,进一步对核心靶点进行网络拓扑分析,利用DAVID数据库对核心靶点进行富集分析,获得白术治疗UC的潜在基因本体(gene ontology,GO)生物进程及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路。[结果]通过SwissADME数据库,评价各分子结构是否满足Lipinski、Ghose等类药规则,筛选得到白术活性成分11种,白术活性成分主要有白术内酯Ⅰ、Ⅱ、Ⅲ、木犀草素、芹菜素等。由TCMSP、Swiss TargetPrediction数据库筛选出白术活性成分的潜在作用靶点144个,DisGeNET、TTD、GeneCards数据库筛选获得UC相关靶点147个。根据度值(degree)筛选得出白术治疗UC的核心靶点58个,主要涉及p53蛋白、神经生长因子受体酪氨酸激酶A(tyrosine kinase A,TrkA)、雌激素受体1(estrogen receptor 1,ESR1)、微小染色体维持蛋白2(microchromosomal maintenance protein 2,MCM2)等。设定错误发生率(false discovery rate,FDR)≤0.05,通过GO生物进程富集分析确定了30个条目,主要包括基因沉默调控、端粒组织、DNA复制依赖性核小体组装、rDNA染色质沉默等。KEGG通路富集结果显示白术治疗UC的潜在通路共48条,主要涉及癌症中的转录失调通路、癌症通路、前列腺癌通路、细胞周期通路等。分子对接结果显示,白术活性成分木犀草素、芹菜素与多个疾病核心靶点蛋白存在潜在结合位点。[结论]白术治疗UC是多成分、多靶点、多途径共同作用的结果,本研究结果为白术的临床应用以及UC相关疾病的基础及临床研究提供了科学依据,同时为新药的研发及应用提供了新思路。     

基于网络药理学探讨健脾祛湿化瘀膏对支气管扩张缓解期的作用机制

[目的]分析健脾祛湿化瘀膏的有效化学成分及作用于人体的靶点蛋白,以探索其治疗支气管扩张缓解期的作用机制。[方法]通过中药系统药理学数据库分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)对健脾祛湿化瘀膏的化学活性物质及作用于人体的靶点蛋白进行检索和筛选,同时应用基因组注释数据库平台(genome annotation database platform,GeneCards)预测疾病靶点,绘制关键化学成分-靶点网络图;通过String数据库平台构建蛋白互作(protein-protein interaction,PPI)网络,寻找PPI核心基因,再进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,找出所涉及的信号通路,构建靶点-信号通路网络图。[结果]通过筛选,共获得健脾祛湿化瘀膏治疗支气管扩张缓解期的关键化学成分107个,共同靶点60个;GO富集分析结果包括营养水平应答、囊泡腔、血红素结合等,KEGG富集分析结果包括晚期糖基化终产物及其受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)信号通路、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路、白介素-17(interleukin-17,IL-17)信号通路等。[结论]健脾祛湿化瘀膏可能通过调节AGE-RAGE信号通路、TNF信号通路、IL-17信号通路等发挥抗感染、抗炎、调节免疫的功能,进而起到治疗支气管扩张缓解期的作用。     

基于网络药理学探讨姜黄-白芍治疗类风湿关节炎协同机制

目的 基于网络药理学方法探讨姜黄-白芍药对治疗类风湿关节炎(RA)的协同机制.方法 通过TCMSP平台和文献资料筛选姜黄-白芍药活性成分及对应的靶点蛋白,应用Cytoscape 3.7.1软件构建药物-成分-靶点网络.在 GeneCards、OMIM、CTD 数据库中检索"Rheumatoid Arthri-tis",获取RA疾病靶点.对药对和RA共同靶点进行PPI网络分析,GO富集和KEGG通路富集分析.结果 获取药对13种活性成分及445个潜在靶点,RA疾病2 060个相关靶点,得到姜黄、白芍、RA三者共同靶点53个,PPI网络中根据自由度(degree)靠前的3个靶点基因为AKT1、TNF、PTGS2,GO富集结果为225个,姜黄与RA相关通路28条,白芍与相关通路74条,其中24条信号通路重合.结论 姜黄-白芍药对可能通过调节AKT1、TNF、PTGS2等靶点,发挥抗氧化、抑制炎症反应、调节免疫功能及调控细胞凋亡等功能协同防治RA.     

基于网络药理学探讨"白术-茯苓"配伍治疗代谢综合征的作用机制

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.     

基于网络药理学探讨四妙丸治疗痛风及高尿酸血症作用机制

目的采用网络药理学的方法,对四妙丸治疗痛风及高尿酸血症的作用机制进行研究探讨。方法通过在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)对四妙丸进行活性成分筛选,运用Cytoscape 3.7.1构建化合物-靶点网络;检索治疗靶点数据库(Therapeutic Target Database,TTD)和DisGenet数据库获取疾病靶标;通过韦恩图,得到疾病与药物的共同靶点;对四妙丸治疗痛风及高尿酸血症的关键靶点进行基因本体(Gene Ontology,GO)功能注释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;构建四妙丸化合物-共同靶点-信号通路网络。结果研究显示共挖掘到四妙丸中64种成分及163个潜在靶点,痛风及高尿酸血症165个相关靶点,得到四妙丸-痛风及高尿酸血症共同靶点9个,共同作用靶点主要富集于533个生物过程和20条信号通路上。结论四妙丸可能是通过调节前列腺素内过氧化物合酶2(Prostaglandin-endoperoxide synthase 2,PTGS2)、前列腺素内过氧化物合酶1(Prostaglandin-endoperoxide synthase 1,PTGS1)、肿瘤坏死因子α(tumor necrosis factor,TNF-α)、白介素1β(interlukin-1β,IL-1β)、过氧化物酶体增殖物激活受体γ(peroxisome proliferative activated receptor gamma,PPARG)等靶点,调控破骨细胞分化、c型凝集素受体信号通路、核转录因子κB(nuclear factor kappa-B,NF-κB)信号通路、白介素17(interlukin-17,IL-17)信号通路等通路,从而发挥抗炎、细胞凋亡、细胞周期调控、抗氧化应激来治疗痛风及高尿酸血症。     

基于数据挖掘和网络药理学的甬派中医治疗糖尿病的用药规律及机制分析

[目的] 基于数据挖掘分析甬派中医治疗糖尿病的用药规律,同时采用网络药理学分析核心药物治疗糖尿病的潜在活性成分及机制。 [方法] 收集宁波市第一医院2016至2020年中药治疗糖尿病的处方,采用中医传承辅助系统构建处方数据库,分析用药规律并筛选核心药物。采用中医药数据和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)以及基因组注释数据平台(Genome Annotation Database Platform,GeneCard)等数据库构建“疾病-核心药物-成分-靶点”网络,采用STRING数据库构建蛋白互作(protein protein interaction,PPI)网络,采用R语言对相关靶点进行核心靶点的基因本体(gene ontology,GO)和京都基因和基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析。 [结果] 共纳入处方430首,其中药性以寒、温、平为主,药味以甘类为主。使用频次最高(＞100次)的中药有甘草、茯苓、陈皮、石斛、白术、黄芪、地黄、党参和枸杞子。关联规则表明,使用频率较高的两药组合有:陈皮-甘草、陈皮-茯苓、白术-茯苓、甘草-茯苓;三药组合为陈皮-白术-茯苓。药物组合网络筛选出核心药物组成为白术-茯苓-陈皮-甘草,发挥益气健脾的功效。网络药理学分析结果表明,核心药物中的32个活性成分与糖尿病靶点相关,在活性成分贡献度排名中,白术和茯苓的成分排名普遍靠前,白术主要成分为白术三醇和苍术酮衍生物,茯苓主要成分为甾醇类,陈皮为柚皮素和甾醇类,甘草以黄酮类成分为主。KEGG结果表明核心药物主要影响脂质和动脉粥样硬化、内分泌抵抗、环磷酸腺苷(cyclic adenosine monophosphate,cAMP)信号通路和晚期糖基化终末产物-晚期糖基化终末产物受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)系统,其中AGE-RAGE系统包含的核心靶点最多,且与糖尿病密切相关。[结论] 甬派中医对糖尿病的治疗以益气健脾为主,同时配合养阴清热,具有多成分、多靶点治疗的特点,其机制可能主要与AGE-RAGE轴密切相关,上述研究为甬派中医治疗糖尿病的方法提供了理论支撑。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

Acupuncture Combined with Spinal Tui Na for Treatment of Primary Dysmenorrhea in 30 Cases

Objective: To observe the therapeutic effects in acupunture treatment of primary dysmenorrhea combined with spinal Tui Na, and study its mechanism. Methods: Thirty cases of the treatment group were treated by acupuncture combined with spinal Tui Na, and thirty cases in the control group were treated by routine acupuncture. Results: The total effective rate was 93.3% in the treatment group, and 73.3% in the control group, with a significant difference between the two groups (P<0.05). Conclusions: Acupuncture combined with spinal Tui Na has good prospects for treatment of primary dysmenorrhea.     

Luo Lingjie's Experience in Treating Chronic Nephropathy

In treating chronic nephropathy,Luo Lingjie,a chief physician,pays attention to regulating the balance between yin and yang,treating infection if present,and removing pathogenic factors.He prescribes gentle drugs and uses carefully strongly warming-tonifying ones,emphasizes the importance of persuading the patient to persist in treatment with medication and nurse one's health for recuperation,and is good at combined use of TCM and western medicine therapy and brings the merits of various therapies into full play,with obvious theraoeutic effects.     

Dr.Zhang Ren's Experience in the Acupuncture Treatment of Different Diseases with the Same Therapeutic Principle

Dr.Zhang Ren,the chief physician,is the chairman of Shanghai Acupuncture and Moxibustion Association.Having been engaged in medicine for about 40 years,he is experienced in treating various intractable diseases.In his long years of clinical practice,he advocates taking the TCM differentiation as the basis to seek for the acupuncture method for treatment of modern intractable diseases.The author of this essay had the fortune to follow Dr.Zhang in study.The following is a summary of Dr.Zhang's experience in the acupuncture treatment for different intractable diseases with the same therapeutic principle.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.