穿心莲的研究及临床开发

概述穿心莲在生药学、化学成分、药理学、临床应用、制剂开发、不良反应等方面的研究进展。穿心莲主要成分为二萜类内酯和黄酮，具有抗菌消炎、抗病毒、抗肿瘤、防治心血管疾病、抗肝损伤、增强免疫、抗生育等多种药理作用，值得进一步研究与开发。     

穿心莲化学成分和药理作用的研究进展

目的现代药理学研究表明穿心莲对心血管系统具有良好的作用。方法通过近年来国内外学者对穿心莲的化学成分、药理作用的研究概况了解穿心莲的作用。结果穿心莲是我国传统中药。其所含化学成分主要有二萜类成分等,现代药理学研究表明穿心莲对心血管系统具有良好的作用。结论现代药理学研究表明穿心莲对心血管系统具有良好的作用。     

穿心莲治疗心脑血管疾病的研究进展

为了综合开发利用穿心莲药用资源,查阅关于穿心莲化学成分、药理作用、临床应用及不良反应方面的文献对穿心莲用于心脑血管疾病进行综述.同时,为穿心莲用于治疗心脑血管疾病提供理论依据.     

穿琥宁注射液不良反应及原因分析

穿琥宁是从爵床科植物穿心莲叶中提取制成的中药制剂，其有效成分是脱水穿心莲内酯琥珀酸半酯单钾盐，其药理作用主要包括：①抗病原微生物的作用。无直接杀菌作用。但可增强吞噬细胞对病原微生物的吞噬作用；②抗心肌缺血和抗心律失常作用。可升高下移的ST段，减少病理性Q波的出现，降低心律失常发生率；③抗血小板凝聚，抑制血栓形成；③解热抗炎；⑤保肝利胆；⑥兴奋垂体-肾上腺皮质系统。     

穿心莲及其制剂的药理作用和临床研究进展

目的：综合开发利用穿心莲资源。方法：查阅献对穿心莲的化学成分、药理作用、临床应用及不良反应进行综述。结果：穿心莲具有很大的药用价值。结论：穿心莲具有开发利用价值。     

穿心莲内酯治疗脓毒症机制的研究进展

穿心莲内酯为中药爵科植物穿心莲的有效成分之一,既往研究提示,穿心莲内酯具有抗氧化、抗炎、抗肿瘤、调节免疫等作用,因其作用靶点及作用途径较多,临床上用于感染性疾病及部分自身免疫性疾病的治疗,已成为脓毒症治疗领域的研究热点,积极研究探讨穿心莲内酯对脓毒症治疗的作用机制,可为脓毒症的中医辅助治疗提供理论依据及策略。     

穿心莲内酯的研究进展

综述穿心莲内酯的稳定性、结构改造、药动学和药效学特点。药理研究表明，穿心莲内酯具有消炎抗菌、抗病毒感染、抗肿瘤、免疫调节、抗心脑血管疾病、保肝利胆等作用。以穿心莲内酯为母核结构进行新的构效研究，将具有广阔的新药开发前景。     

穿心莲内酯衍生物抗肿瘤、解热抗炎构效关系研究进展

目的对近年来穿心莲内酯衍生物抗肿瘤、解热抗炎的构效关系研究进展综述,为穿心莲内酯的进一步研究提供思路。方法对相应文献进行归纳、总结和综述。结果穿心莲内酯及其衍生物发挥抗肿瘤活性的必需基团是完整的α-亚烷基-γ-丁内酯,Δ12,13双键,Δ8,17双键或成环及C14羟基等活性基团;而α-亚烷基-γ-丁内酯环打开与否和抗炎无关,穿心莲内酯及其衍生物的双键位置决定其抗炎作用,具有环内双键的化合物抗炎作用强于具有环外双键的化合物。结论穿心莲内酯衍生物具有良好的开发前景,应加强其衍生物与构效关系的研究。     

穿心莲内酯对雄性大鼠的生殖毒性和抗生育特性研究——对睾丸和附睾尾中精子的影响

穿心莲内酯是穿心莲Andrographispaniculata中主要次生代谢物之一。曾报道它对几种实验性肝损伤有保护作用,雄性大鼠口服穿心莲干叶粉末,显示阻止精子生成的作用。作者研究了该化合物对雄性大鼠生殖毒性和抗生育能力。     

穿心莲内酯对神经退行性疾病的作用及其机制研究进展

氧化应激、线粒体功能障碍以及炎症反应是神经退行性疾病如阿尔兹海默病（Alzheimer’s disease,AD）和帕金森病（Parkinson’s disease,PD）等发生和发展的关键环节。因此,保护线粒体、缓解氧化应激和抑制炎症对防治此类疾病具有重要意义。穿心莲内酯是穿心莲的主要有效成分,具有较好的抗炎、抗肿瘤、抗病毒、抗HIV和保肝等生物活性。近年来,越来越多研究证实穿心莲内酯在神经退行性疾病方面有着良好的应用前景,主要通过诱导线粒体自噬而保护线粒体稳态、抑制炎症小体的活化;清除活性氧,保护线粒体,或抑制小胶质细胞炎症反应保护神经元细胞。文章总结了近十年来穿心莲内酯在神经退行性疾病如AD、PD和脑缺血损伤等方面的药理活性及机制研究,以期为穿心莲内酯的研究开发和在神经退行性疾病中的临床应用提供参考。     

The acute effects of cannabinoids on memory in humans: a review

Rationale Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors’ function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects.Objective The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings.Results Acute administration of Δ-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels.Conclusions This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and preclinical literature.     

急性创伤性血胸凝血功能异常的临床研究

目的探讨急性创伤性血胸患者的凝血功能变化特点及与出血量严重程度、预后的关系。方法1将126例急性创伤性血胸患者分为小量、中量、大量3组，测定患者入院当时、24 h、及72 h的血浆凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原（FIB）、血小板（BPC）值，并与43例健康对照组比较。2入院、24 h、72 h将各组血胸的凝血指标异常发生情况进行比较。结果1各型血胸中入院时PT、APTT、FIB、BPC均有异常，随着胸腔出血量增大，PT、APTT均升高，FIB、BPC降低。2入院24 h各组血胸的凝血指标异常发生率无明显差异。3入院72 h大量血胸组患者的凝血指标异常发生率和中、小量血胸组相比有明显差异。结论小量血胸患者的凝血功能无异常改变，中、大量血胸患者的凝血功能异常，且与血胸量程度相关，大量血胸组患者的入院72 h凝血指标异常发生率显著提高，可为急性创伤性血胸的治疗和判断预后提供依据。     

关于基本药物剂型、规格、包装遴选标准的研究

目的：研究建立基本药物剂型、规格、包装的遴选标准。方法：采用文献研究法系统梳理了1977—2009年世界卫生组织（WHO）关于基本药物遴选原则和标准的调整、变化和发展,并研究了WHO的基本药物目录和90个国家的基本药物目录,归纳了WHO关于剂型、规格、包装的遴选标准,以此为基础设计问卷,采用调查问卷法和座谈法,对行政管理人员、基层医疗机构管理者和医生、企业进行了调查,经整理分析,提出了遴选标准。结果：药物的安全有效性、剂型的经济和方便性、临床单次给药剂量、剂量调整幅度、临床疗程和包装的经济性、耐用性,是基本药物剂型、规格、包装遴选应当首先关注的方面。结论：提出了关于基本药物剂型、规格、包装的遴选标准,并认为具有操作性。     

基于CiteSpace的国内外抗菌药物透过血脑屏障的研究进展及可视化分析

目的 利用科学文献可视化分析软件CiteSpace对国内外抗菌药物透过血脑屏障的研究现状、研究热点和发展趋势等进行客观全面的展示与分析，为临床用药提供有用的指导与参考。方法 以Web of Science数据库、CNKI数据库为检索对象，纳入建库至今发表的与抗菌药物透过血脑屏障研究相关的文献，使用Excel对原始数据进行初步的文献计量分析，使用CiteSpace对关键词、作者、期刊、机构、国家等进行科学文献可视化分析，形成相关的可视化科学网络图谱。结果 抗菌药物透过血脑屏障的研究主要集中在血脑屏障的结构与功能、中枢神经系统感染的预防与治疗、抗菌药物的PK/PD、新型抗菌药物、抗菌药物载体等方面，研究热度不断上升。美国、欧洲、日本都在抗菌药物透过血脑屏障研究方面有着突出的贡献，但是各国、各机构之间的合作交流并不密切。国内研究相比国外研究，存在起步时间晚、研究数量少、研究质量不高的缺陷，无论是发文量还是文章质量均落后于国外，需要加强与国际的合作交流与学习。结论 目前，抗菌药物透过血脑屏障的研究日益受到人们的重视，欧美与日本对抗菌药物透过血脑屏障的研究处于世界领先水平。国内研究与国外仍存在很大差距，需要加大对抗菌药物透过血脑屏障研究的投入，促进临床合理用药。     

不同浓度呋喃酮C-30对鲍曼不动杆菌ATCC19606菌毛及生物被膜作用的研究#br#

目的 通过分析鲍曼不动杆菌菌毛编码及调节基因的表达情况,探究不同浓度呋喃酮C-30对鲍曼不动杆菌ATCC19606菌毛及生物被膜形成的作用。方法 聚合酶链反应II检测菌株菌毛编码及调节基因的表达情况。不同浓度呋喃酮C-30下Real-time法检测鲍曼不动杆菌ATCC19606菌毛编码和调节基因表达水平、透射电镜下菌毛结构以及结晶紫染色法检测生物被膜的量。结果 csuA/B、csuA、csuB、csuC、csuD、csuE、bfmS和bfmR基因扩增阳性率分别为100%、7.14%、78.57%、89.29%、39.29%、82.14%、85.71%和85.71%。1/4MIC和1/2MIC浓度的呋喃酮C-30能够显著抑制鲍曼不动杆菌ATCC19606菌毛编码及调节基因的表达和菌毛、生物被膜的形成,浓度越大、抑制作用越明显。 结论     

2型糖尿病大鼠主动脉内皮细胞氧化损伤及缬沙坦的保护作用

目的探讨2型糖尿病大鼠氧化应激与主动脉内皮细胞损伤的关系,观察缬沙坦对两者的影响。方法SD大鼠,用长期高能量饮食加小剂量注射链脲佐菌素(STZ)的方法复制模型。注射STZ12wk末,将大鼠分为3组:正常组、糖尿病组、缬沙坦治疗组(24mg·kg-1·d-1,灌胃给药8wk)。在注射STZ12和20wk末,检测大鼠的内皮依赖性血管舒张反应及主动脉内皮形态,血清超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性,丙二醛(MDA)和一氧化氮(NO)含量,以及主动脉一氧化氮合酶(NOS)基因表达情况。结果①12wk末,糖尿病大鼠主动脉对低浓度乙酰胆碱(ACh)舒张反应减弱,局部内皮隆起,血清SOD、GSH-Px活性增强,MDA和NO含量增加,主动脉iNOS mRNA表达明显上调,eNOS mRNA表达无明显改变。②20wk末,糖尿病大鼠主动脉对各浓度ACh的反应性均减弱,主动脉内皮变性、坏死,血清SOD、GSH-Px活性减弱,MDA含量进一步增加,NO含量下降,主动脉iNOS mRNA表达仍升高,eNOS mRNA表达降低,缬沙坦治疗后能减轻主动脉病变,改善血清SOD、GSH-Px、MDA、NO及主动脉NOS mRNA表达的异常。结论糖尿病大鼠的氧化应激和NO系统的紊乱参与了主动脉病变过程,增强机体抗氧化能力及调节NO生成可能是缬沙坦发挥主动脉保护作用的机制之一。     

STAT3抑制剂及烟酰胺联合用药对肝癌HepG2细胞增殖的抑制作用及机制研究

目的　探究STAT3抑制剂（Stattic和S3I-201）以及烟酰胺腺嘌呤二核苷酸（NAD）前体烟酰胺联合用药对肝癌HepG2细胞增殖的影响及机制。方法　以肝癌细胞株HepG2为模型,使用STAT3抑制剂、烟酰胺以及两者联合处理细胞,通过细胞计数、Western blot和qPCR等检测药物对细胞增殖、STAT3表达、STAT3下游靶基因［锌指转录因子1（SNAIL1）、血管内皮生长因子A（VEGFA）、锌指结合蛋白1（ZEB1）］表达和与细胞增殖［微小染色体维持蛋白7（MCM7）、增殖标志物Ki-67（MKI67）、Myc原癌基因蛋白（MYC）］、细胞凋亡［B淋巴细胞瘤2相关X蛋白（BAX）、B淋巴细胞瘤-2（BCL-2）、髓样细胞白血病蛋白1（MCL-1）］、上皮-间充质转化［紧密连接蛋白-1（TJP1）、母亲DPP同源物3（SMAD3）］以及糖代谢［己糖激酶2（HK2）、磷酸果糖激酶（PFKL）、M型丙酮酸激酶（PKM）、葡萄糖转运蛋白1（GLUT1）、乳酸脱氢酶A（LDHA）］相关基因的mRNA表达水平的影响。结果　STAT3抑制剂和烟酰胺处理均能降低STAT3磷酸化水平,抑制细胞增殖,降低细胞增殖、抗凋亡、上皮-间充质转化以及糖代谢相关基因表达水平,上调促凋亡相关基因表达水平。并且,联合用药对STAT3磷酸化水平、细胞增殖以及上述生物过程相关基因的表达水平影响更显著。结论　STAT3抑制剂和烟酰胺可抑制肝癌细胞增殖,并且联合用药效果更显著。这种抑制作用可能与促进凋亡和抑制上皮-间充质转化及糖酵解有关。     

Early drug discovery and the rise of pharmaceutical chemistry

Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid‐nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative‐hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin‐offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal‐tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p‐nitrophenol, both of which were byproducts from coal‐tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history. Copyright © 2011 John Wiley & Sons, Ltd.     

Antagonism of cholecystokinin-like peptides by opioid peptides, morphine or tetrodotoxin

Morphine, beta-endorphin, Met-enkephalin, and Leu-enkephalin antagonized intestinal actions of cholecystokinin octapeptide (CCK-8), caerulein, and pentagastrin in a manner partly suggesting physiologically competitive antagonism. Further, these acidic peptides (CCK-8, caerulein, pentagastrin) were much more sensitive to the actions of opioids than was angiotensin. Tetrodotoxin also caused changes in the concentration-effect curves, but these were different from the shifts due to the opioids and differentiated between CCK-8, caerulein, and pentagastrin. Naloxone did not modify the response to CCK-8 and caerulein, but completely abolished the antagonistic influence of the opioids. The potencies of morphine and the opioid peptides as antagonists of CCK-8, were of nearly the same order of magnitude. This and the presence in gut and brain of both CCK-like and opioid peptides suggests the hypothesis that these two groups of peptides interact on both myenteric and central nervous system receptors, and thus are directly involved in the regulation of both intestinal motility and satiety.     

Depletion of securin increases arsenite-induced chromosome instability and apoptosis via a p53-independent pathway.

Arsenic is a pathologic factor of cardiovascular diseases and cancers; nevertheless, it also acts as an anticancer agent effective on acute promyelocytic leukemia and multiple myeloma. Securin, a proposed proto-oncogene, regulates cell proliferation and tumorigenesis. However, roles of securin on the arsenic-induced cell cycle arrest and apoptosis remain unknown. In this study, the effects of sodium arsenite on the expression of securin in two tissue types of cell lines, the vascular endothelial and colorectal epithelial cells, were investigated. Arsenite (8-16 microM, 24 h) increased the cytotoxicity, apoptosis, and growth inhibition in both endothelial and epithelial cells. The levels of phospho-CDC2 (threonine-161), CDC2, and cyclin B1 proteins were decreased, and the G2/M fractions were increased by arsenite. Concomitantly, arsenite markedly diminished the securin protein expression and induced the abnormal sister chromatid separation. The depletion of securin proteins increased the induction of mitotic arrest, aberrant chromosome segregation, and apoptosis after arsenite treatment. p53, a tumor suppressor protein, balances the cell survival and apoptosis. Arsenite raised the levels of phospho-p53 (serine-15) and p53 (DO-1) proteins in both the securin-wild-type and -null cells. The p53-functional cells were more susceptible than the p53-mutational cells to arsenite on the cytotoxicity and apoptosis. Besides, arsenite decreased the levels of securin proteins to a similar degree in both the p53-functional and -mutational cells. Together, it is the first time to demonstrate that the inhibition of securin expression induced by arsenite increases the chromosomal instability and apoptosis via a p53-independent pathway.