川芎嗪的治疗作用研究

中药川芎具有行气活血、祛风止痛、温通血脉之功效。川芎嗪为川芎的主要成分，是一种吡嗪类生物碱。现代医学表明川芎嗪（TMP）具有解痉、降低血管阻力、保护血管内皮细胞、抗血小板凝集、Ca^2＋拮抗、抗纤维化等作用。边晓丽等旧。通过实验发现TMP及其代谢产物均具有很强的羟自由基清除作用。临床广泛用于充血性心力衰竭、器官组织纤维化治疗。TMP明显改善急性心肌梗死血管内皮依赖性血管舒张功能，对急性心肌梗死溶栓后心肌微循环有明显保护作用。近年来，有关TMP的研究证实，TMP含数十种化学成分，能抑制血小板的激活、升高血栓素A2水平、抑制血细胞在缺血区的浸润和黏附，提高超氧化物歧化酶（SOD）和一氧化氮合成酶（NOS）的活性、增加冠脉流量、改善心肌供氧、降低心肌耗氧的作用，治疗缺血性脑血管病及冠心病效果良好。[第一段]     

抗肝纤维化药物研究现状

肝纤维化是大多数慢性肝病所共有的病理特征 ,其防治是当今肝病治疗的难点之一。本文就肝纤维化的发生机制 ,抗肝纤维化研究靶标 ,天然肝纤维化调控因子和国内外抗肝纤维化药物研究现状等方面进行综述     

基于抗氧化应激作用改善肝纤维化的天然产物的研究概况

目的:总结基于抗氧化应激作用改善肝纤维化的天然产物的研究概况,为天然产物的开发及应用提供参考。方法:以"天然产物""肝纤维化""氧化应激""肝损伤""Natural products""Hepatic fibrosis""Oxidative stress""Liver injury"等为关键词,组合查询2000年1月-2019年6月中国知网、万方数据、维普网、PubMed等数据库中的相关文献,归纳总结可通过抗氧化应激作用改善肝纤维化的天然产物种类,并明确其具体抗氧化应激作用机制。结果与结论:共检索到相关文献745篇,其中有效文献56篇。基于抗氧化应激作用改善肝纤维化的天然产物有黄酮类化合物(如黄芩素、高良姜素、水飞蓟素、五味子素等)、萜类化合物(如甘草酸苷、甘草次酸、黄芪甲苷、熊果酸等)、生物碱类化合物(如苦参碱、小檗碱、杏黄罂粟碱等)、多酚类化合物(如姜黄素、白藜芦醇、迷迭香酸等)等。上述天然产物主要通过增强肝组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GST)的活性,降低活性氧(ROS)的活性和丙二醛的水平,抑制核转录因子κB(NF-κB)信号通路等发挥抗氧化应激作用改善肝纤维化。目前,天然产物基于抗氧化应激作用改善肝纤维化的研究主要以动物模型为主,因此,在后续研究中可探索其临床应用价值,以期为临床使用天然产物治疗肝纤维化提供参考。     

心肌纤维化药物治疗的研究进展

各种原因(如炎症、缺血、高血压等)引起的心肌损害，如果病变持续，终将导致心肌纤维化的发生。故防治心肌纤维化是当前医学研究的重点和热点。本文综述了心肌纤维化的实验室检测以及多种药物治疗心肌纤维化的进展及其作用机制。     

心肌纤维化的诊断与衡量

心肌纤维化参与了多种心血管疾病的发生发展。心肌纤维化改变了心肌原本的结构，可能导致心脏舒缩功能障碍，增加不良心血管事件发生的风险，对心血管疾病患者的临床治疗及预后产生着很大的影响。早期发现、干预心肌纤维化就显得尤为重要，该文就心肌纤维化的诊断与衡量进行综述。     

鹿茸的活性物质及药理作用的研究进展

对近年来鹿茸的活性物质及其对保护损伤心肌,治疗神经系统损伤和骨质疏松,抗肝纤维化、抗关节炎、抗缺氧、抗疲劳等方面药理作用的研究进展进行综述,为进一步开发利用鹿茸提供参考。     

松弛素的生物学作用及其药用前景

松弛素是与胰岛素类似的肽类激素,具有广泛的生物学作用,包括在哺乳动物妊娠和机体老化时维持内环境的稳定、抗炎、心肌保护、扩张血管、促进伤口愈合等作用,尤为重要的是具有抗纤维化作用。各种原因引起的心脏、肾脏病变最终均可发生纤维化,导致结构改变、功能丧失,因此通过有效的抑制纤维化过程,是挽救脏器功能的重要措施,而松弛素的抗纤维化作用可能成为未来抗纤维化治疗的有效措施。     

丹参酮ⅡA磺酸钠注射液治疗肝硬化并冠心病60例疗效观察

目的观察经静脉输注丹参酮ⅡA磺酸钠注射液治疗肝硬化代偿期，失代偿期合并冠心病的临床疗效。方法治疗组静脉输注丹参酮ⅡA磺酸钠注射液，对照组静脉输注丹参注射液，观察两组治疗前后的临床症状，体征，肝功能，肝纤维化指标，心电图等。结果治疗组治疗后与治疗前比较症状，体征，肝功能，肝纤维化指标，心电图改善比较明显。治疗组与对照组治疗后的肝纤维化指标差异无统计学意义（P〉0．05）。结论丹参酮ⅡA磺酸钠注射液具有一定的活血化淤，抗肝纤维化，改善心肌缺血，提高心肌缺氧能力的作用。     

依那普利抗异丙肾上腺素诱导的心肌纤维化作用及机制

目的观察依那普利(enalapril,Ena)抗异丙肾上腺素(Isoprenaline,Iso)诱导的心肌纤维化作用并探讨其作用机制。方法异丙肾上腺素皮下注射致心肌纤维化模型,经Ena低、中、高(2.5、5.0、10.0 mg.kg-1)3个剂量组和阳性对照药卡托普利(100.0 mg.kg-1)治疗后观察其对心肌组织胶原变化、心室重量(HW/BW)和心室重量指数(LVI)、羟脯氨酸含量及免疫组化和Western blot检测TGF-β1表达的影响。结果Ena不同剂量组均能够降低心肌组织胶原含量(P<0.05或P<0.01),降低HW/BW和LVI(P<0.05或P<0.01),降低羟脯氨酸含量(P<0.05或P<0.01),减少TGF-β1在心肌组织中的表达(P<0.05或P<0.01),减轻心肌纤维化。结论Ena通过抑制TGF-β1表达抗Iso诱导的心肌纤维化。     

曲美他嗪对缺血性心肌病患者的心肌纤维化和血浆脑钠肽水平的影响

缺血性心肌病(ICM)是冠心病的一种特殊类型,冠状动脉粥样硬化造成心肌细胞持续缺血,心肌纤维化,心肌细胞功能低下,影响心肌收缩功能和心室负荷,而心室负荷过重会导致脑钠肽(BNP)过度分泌。曲美他嗪能有效优化心肌氧代谢,因而具有较好的抗心绞痛和心肌保护作用,本文现将曲美他嗪治疗缺血性心肌病的药理作用机制,及对患者心肌纤维化和血浆脑钠肽水平的影响作简要综述。     

Vasopeptidase inhibition reverses myocardial vasoactive intestinal peptide depletion and decreases fibrosis in salt sensitive hypertension

We have shown previously that the concentration of Vasoactive Intestinal Peptide (VIP) in the heart is inversely correlated with the degree of fibrosis in a number of experimental models of early myocardial fibrosis. Vasopeptidase inhibition and angiotensin converting enzyme inhibition both decrease myocardial fibrosis. In this study, we sought to determine whether this myocardial protective effect might reflect increased VIP concentrations in the heart. We compared the effects of 4 weeks treatment of the vasopeptidase inhibitor omapatrilat and the angiotensin converting enzyme inhibitor enalapril on the degree of fibrosis and the concentration of VIP in the heart in salt sensitive hypertension induced by treatment with L-nitro-omega-methylarginine (L-NAME). Systolic blood pressure decreased in both treatment groups compared with control (omapatrilat P<0.005; enalapril P<0.001). Myocardial fibrosis was less for omapatrilat than control (P<0.0005) and enalapril (P<0.0005) groups. Myocardial VIP was greater in omapatrilat than in controls (P<0.005) and enalapril-treated rats (P<0.05). We conclude that vasopeptidase inhibition exerts a greater myocardial protective effect than angiotensin converting enzyme inhibition. Further, this myocardial protective effect is associated with increased VIP in the heart suggesting a pathogenetic role for VIP depletion in the development of fibrosis in the heart.     

Natural products of dietary origin as lead compounds in virtual screening and drug design

Natural products have been found to be useful in the treatment of several diseases across the ages. In this article, we review the use of natural products, obtained from dietary sources, as lead compounds in developing novel therapeutic agents. These compounds have shown tremendous promise in the prevention and as well as treatment of a variety of chronic ailments. In addition, to being patentable and biocompatible, these compounds are a rich source of novel scaffolds to invigorate the pipelines of the pharmaceutical industry. In this communication, we also focus on studies which show how natural products have proved useful as lead compounds in virtual screening and structure-based drug design programs. Natural dietary constituents, such as resveratrol, curcumin and caffeine as well as other compounds, are discussed to illustrate this approach.     

天然产物在黑色素瘤防治中的研究进展

恶性黑色素瘤是一种高致死性的皮肤肿瘤,发病率在全世界范围内呈上升趋势。恶性黑色素瘤严重至危及生命的原因主要是其具有较强的侵袭转移能力。出现远处转移病灶的患者,即使采用最新的治疗,仍会出现复发现象,中位生存期仅有数月。目前关于黑色素瘤的防治手段主要包括手术切除、化学疗法、免疫治疗及靶向治疗。然而,这些治疗策略会导致耐药性和严重的不良反应。近年来,越来越多的研究发现天然产物具有良好的抗黑色素瘤活性,包括抑制肿瘤生长、诱导细胞凋亡、抑制血管生成和转移、消除肿瘤干细胞等。此外,许多研究报告了天然产物和传统抗黑色素瘤药物的联合作用增强了治疗效果。本文就天然产物对黑色素瘤的预防潜力、治疗效果进行简要总结讨论。     

氯沙坦对老年高血压患者心肌纤维化改善效果的临床研究

目的 观察氯沙坦对老年高血压患者心肌纤维化的影响.方法 对44例老年高血压心肌纤维化患者口服氯沙坦(50 ～100 mg/d)治疗12～16个月,观察治疗前后患者血压和心肌纤维化改善情况.采用酶联免疫法在治疗前后各测一次血浆中Ⅲ型胶原前肽、层粘连蛋白.结果 氯沙坦治疗后血压明显下降(P＜0.01),心率无明显变化(P＞0.05),心肌纤维化指标:Ⅲ型前胶原氨基末端肽(PⅢP)、层粘连蛋白(LN)均明显降低(P＜0.05).结论 氯沙坦在有效降压的同时,部分逆转或减轻心肌纤维化,对心率无明显影响.     

Cytoprotection by natural and synthetic polyphenols in the heart: novel mechanisms and perspectives

While many naturally occurring polyphenols have been shown to have therapeutic benefits against myocardial injury following ischemia-reperfusion in various experimental models, our studies have demonstrated that synthetic flavonoids may also have potent cardiac cytoprotective actions. Together with the results reported in the literature, we suggest that synthetic polyphenols may be an ideal replacement for natural compounds in the development of myocardial protective drugs. Polyphenols exert myocardial protective effects via antioxidant activities, preservation of nitric oxide, antiinflammatory activities and modulation of matrix metalloproteinases. Recent studies have identified some novel mechanisms that may also contribute to polyphenol-induced myocardial protection, including prevention of mitochondrial dysfunction, pharmacological preconditioning, and modulation of the function of enzymes involved in epigenetic modifications such as histone acetyltransferases. In addition to the protective effects against acute myocardial injury, there has been experimental evidence showing that polyphenols may also modulate the development of cardiac hypertrophy, ventricular remodeling and fibrosis after myocardial infarction.     

Natural products and derivatives as leads to cell cycle pathway targets in cancer chemotherapy

The influence of natural products upon drug discovery in general has been quite impressive; one only has to look at the number of clinically active drugs that are in use in cancer therapy to see how many either are natural products or have a natural pro-duct pharmacophore. What is now becoming quite apparent is that materials from natural sources are excellent probes (indicators) for cellular targets that when modulated, may well have a deleterious effect upon the cycling of a tumor cell through the conventional cell cycle. If the particular target is not expressed in normal cell cycling, then a directed "perturbation" of the tumor cell's cycle may well lead to a novel method of treatment for specific tumor types. In this review we have not attempted to be exhaustive but have given a current overview of how natural products from marine, microbial and plant sources have permitted in-depth analyses of various parts of the cell cycle under varying conditions with the ultimate aims of attempting to "control or perturb" the cycling of tumor cells in a fashion that permits their ultimate removal via cellular death, with a minimum of trauma to the host.     

Natural products--the future scaffolds for novel antibiotics?

Natural products have played a pivotal role in antibiotic drug discovery with most antibacterial drugs being derived from a natural product or natural product lead. However, the rapid onset of resistance to most antibacterial drugs diminishes their effectiveness considerably and necessitates a constant supply of new antibiotics for effective treatment of infections. The natural product templates of actinonin, pleuromutilin, ramoplanin and tiacumicin B, which are compounds undergoing clinical evaluation, represent templates not found in currently marketed antibacterial drugs. In addition, the new templates present in the recently discovered lead antibacterials arylomycin, GE23077, mannopeptimycin, muraymycin/caprazamycin, nocathiacin and ECO-0501, are discussed. Despite extensive efforts to identify antibiotic leads from molecular targets, only the peptide deformylase inhibitor LBM-415 is currently in clinical trials. It is proposed that new antibacterial assays which combine cell-based screening with molecular targets could offer better prospects for lead discovery.     

曲尼司特对糖尿病大鼠心肌纤维化的作用

目的探讨曲尼司特对糖尿病大鼠心肌纤维化的作用及其可能机制。方法健康♂SD大鼠一次性尾静脉注射链脲佐菌素制备糖尿病大鼠模型,随机分为糖尿病组(DM组),曲尼司特低剂量组(Tra1)及高剂量组(Tra2),造模成功72 h后每天ig给予曲尼司特100 mg.kg-1.d-1及200 mg.kg-1.d-1,同时设立对照组(NC组)。饲养12周。测量血糖、心脏质量指数、血浆及心肌血管紧张素Ⅱ水平;Masson染色观察心脏形态学变化,免疫组化法和Western印迹法检测心肌组织CTGF、Ⅰ型、Ⅲ型胶原蛋白表达。结果①与NC组相比,DM组大鼠心脏质量指数、血浆及心肌血管紧张素Ⅱ(AngⅡ)水平明显升高(P<0.01),心肌间质纤维化明显,心肌CTGF蛋白、Ⅰ型、Ⅲ型胶原蛋白表达增加;②与DM组比较,Tra1、Tra2组大鼠心脏质量指数、血浆及心肌AngⅡ水平均明显下降(P<0.05),心肌间质纤维化减轻,心肌CTGF、Ⅰ型、Ⅲ型胶原蛋白表达减少。结论曲尼司特能降低糖尿病大鼠心肌AngⅡ水平,减少CTGF、Ⅰ型、Ⅲ型胶原蛋白的表达,从而抑制糖尿病大鼠心肌纤维化。     

吡非尼酮的药理学及疾病治疗学研究进展

吡非尼酮是近年来上市用于治疗特发性肺纤维化的药物。研究证实该药具有抑制胶原合成、抗炎和抗氧化的作用。吡非尼酮作为一种广谱的抗纤维化药物,在特发性肺纤维化、肝纤维化、肾纤维化、心脏组织纤维化、多发性硬化症、神经纤维瘤、子宫肌瘤、恶性胶质瘤的治疗和器官移植纤维化的预防方面均具有广阔的应用前景。     

A novel anti-fibrotic agent, baicalein, for the treatment of myocardial fibrosis in spontaneously hypertensive rats

Myocardial interstitial fibrosis causes left ventricular stiffness and diastolic dysfunction. Despite its clinical significance, treatment options are limited. The flavonoid baicalein, extracted from roots of a Chinese medicinal plant, Scutellaria baicalensis Georgi was shown to inhibit liver fibrosis. This study sought to investigate whether chronic treatment with baicalein could attenuate myocardial fibrosis in spontaneously hypertensive rats (SHR). SHR were treated daily with baicalein while the control group received vehicle. At the end of study, SHR control group developed significant myocardial fibrosis that was attenuated by baicalein treatment for 4 and 12 weeks. Rats treated with baicalein were protected against an increase in heart to body weight ratio, plasma level of brain natriuretic peptides, intraventricular septum thickness, myocardial collagen volume of left ventricle (all P<0.05, respectively). The antifibrotic effects of baicalein were further illustrated by the suppressed expression of left ventricle pro-collagens I and III accompanied by the decreased expression of 12-lipoxygenase, and by reduced expression and activity of matrix metallopeptidase 9 and extracellular signal-regulated kinases. The present results show for the first time that baicalein can inhibit cardiac fibrosis in hypertensive rats.