抗菌肽抗菌机制的研究进展

抗菌肽是广泛存在于生物体内的一类小分子多肽,是生物固有免疫系统的重要组成部分.抗菌肽不仅能够有效杀灭细菌,而且还对真菌、病毒、寄生虫甚至肿瘤细胞都具有一定的杀伤作用.抗菌肽因其作用迅速、广谱抗菌、不易产生耐药性等诸多特点,已成为医药卫生、畜牧养殖、水产动物等领域研究的热点.本文就当前抗菌肽抗菌机制的研究进展作一综述.     

女性生殖道内β防御素类型与作用

β-防御素是广泛分布于动物黏膜上皮中的一类重要抗菌肽,具有广泛的抗细菌、抗真菌、病毒等作用,对于肿瘤细胞杀伤、参与先天性机体免疫具有重要意义。本文对女性生殖道内β-防御素的分布、特征、作用、诱导调控等进行综述,为相关研究提供资料。     

新城疫病毒诱导肿瘤细胞凋亡的实验研究

目的：研究新城疫病毒Lasota株（NDV－L）杀伤肿瘤细胞及诱导肿瘤细胞凋亡的作用。方法：通过噬斑形成单位、HA效价、MTT法等方法检测NDV－L对细胞的杀伤作用；通过Giemsa's染色法、倒置相差显微镜、透射电镜、DNA凝胶电泳、流式细胞仪检测NDV－L诱导肿瘤细胞凋亡的作用。结果：NDV对肿瘤细胞有选择性杀伤作用。经NDV－L诱导后，肿瘤细胞呈现典型的凋亡特征。结论：NDV除通过自身复制直接杀伤肿瘤细胞外，还具有诱导肿瘤细胞凋亡的作用。     

抗菌肽作用机制及应用研究进展

在这抗生素耐药性病菌不断出现的时代,新型抗菌药物的发现已迫在眉睫。而抗菌肽为大多数生物对入侵病原体的自然防御系统的重要组成部分,具有独特的抗菌作用机制,迅速杀菌且不易引发细菌的耐药性,可单独或与抗生素联合使用杀伤病原体,是一类极具发展潜力的生物药物。本文根据抗菌肽的理化性质,作用机制及抗菌肽的设计等进行综述,并对几种有前景的抗菌肽作一简单介绍。     

准确把握抗肿瘤化疗药物功效与毒性"临界点"至关重要

使用抗肿瘤化疗药的理想状态是对肿瘤细胞有选择性毒性作用,将其最大限度地杀灭,而对正常细胞无伤害。但实际情况并不是人们想象那样,通常抗肿瘤药物既杀伤肿瘤细胞,也对正常细胞有杀伤作用。如何处理好化疗药物杀伤肿瘤细胞和正常细胞的临界点,使化疗药物的作用既能杀死肿瘤细胞,又最大程度地保护正常细胞成为人们关心的话题,本刊记者带着有关问题采访了北京大学附属肿瘤医院的赵军医生。     

家蝇抗菌肽抗菌活性及抗菌机制的初步研究

目的　研究家蝇抗菌肽的抗菌活性及抗菌机制。方法　用损伤感染的方法诱导家蝇幼虫表达抗菌肽 ,通过 Sephadex过滤层析和 HL PC技术纯化提取 ,用平板法和稀释法作抗菌活性试验 ,并用电子扫描技术研究抗菌肽的抗菌机制。结果　家蝇抗菌肽对铜绿假单胞菌、大肠埃希氏菌、耐甲氧西林金黄色葡萄球菌( MRSA)均有明显的抗菌活性。大肠埃希氏菌与 5 0 μg/ml的纯化抗菌肽溶液一起 37℃孵育 6 0 min后 ,大肠埃希氏菌不能存活。经电镜扫描观察发现 ,细菌的细胞膜出现破损和穿孔现象。结论　家蝇抗菌肽具有明显的广谱抗菌活性 ,对阴性杆菌和阳性球菌均有杀伤作用。抗菌肽的抗菌机制是通过破坏细菌的细胞膜而杀伤细菌的     

肽类抗生素对细胞选择性作用研究进展

抗菌肽是一种广泛存在于生物界的抵抗病原微生物入侵的重要防御分子。抗菌肽具有广谱抗细菌、真菌、肿瘤细胞等活性，具有自身随着物种适应环境而产生的结构多样性以及具有区别于传统抗生素的杀菌机理的独特性，是一类极有潜力的肽类抗生素。不同抗菌肽对不同类型靶细胞表现出活性上的巨大差异，即是抗菌肽作用的选择性，这种作用的选择性受到多种因素的影响。探讨抗菌肽作用细胞的机理，特别是选择性作用的机理将有助于设计出活性更高的新型肽类抗生素。本文主要从细胞表面结构特异性、抗菌肽自身结构特点阐述近年来抗菌肽活性与选择性作用研究的新进展。     

尿素注射液对体内外肿瘤细胞杀伤作用的实验研究

探讨尿素注射液对体内外肿瘤细胞杀伤率和尿素静脉注射对机体代谢的影响。取处于生长期的胃癌823细胞株，加入尿素注射液观察72h，根据细胞形态和LDH的释放量确定杀伤效果。对致瘤小鼠腹腔注射尿素观察抑制肿瘤效果；家兔静脉注射尿素液观察对体内生化代谢指标的影响。适当浓度尿素注射液在一定时间内可大量杀伤肿瘤细胞，体内观察该药对致瘤小鼠能明显杀伤肿瘤细胞，延长动物生存时间，该药对体内生化代谢指标可产生一定影响。尿素注射液对体内外肿瘤细胞均有杀伤作用，杀伤效果与浓度成正相关，该药静脉注射对体内生化代谢指标有一定影响。     

灰树花β多糖协同化疗药物抗肿瘤作用及其分子机理初探

目的探讨灰树花β多糖在抗肿瘤细胞中的作用和协同化疗药物增加其杀伤肿瘤细胞的作用。另外通过对p53和M DM 2的研究,发现了两者协同作用的分子机理。方法用CCK-8方法测定了灰树花β多糖协同化疗药物处理HCT 116后的细胞存活率(cell surv iva l rate,CSR);用PCR的方法测定了p53、M DM 2基因的表达。结果(1)灰树花β多糖对肿瘤细胞的直接杀伤作用高于灵芝多糖。(2)灰树花β多糖协同化疗药物增强其对肿瘤细胞的杀伤作用。(3)灰树花β多糖协同化疗药物的分子机理和抑制抑癌基因p53的拮抗物M DM 2基因的表达相关。结论灰树花β多糖具有直接杀伤肿瘤作用和化学药物协同抗肿瘤作用。     

槲寄生凝集素对肿瘤细胞细胞周期的影响

目的通过体外实验研究槲寄生凝集素对肿瘤细胞的细胞毒性作用。方法采用MTT比色分析法测定槲寄生凝集素注射液对肿瘤细胞生长曲线的影响 ;采用流式细胞仪技术检测槲寄生凝集素注射液对肿瘤细胞细胞周期的影响。结果和结论槲寄生凝集素注射液对肿瘤细胞有剂量依赖性杀伤作用     

Antimicrobial peptides in oral cancer

There is increasing evidence that antimicrobial peptides (AMPs) are differentially regulated in cancers such as oral squamous cell carcinomas (OSCC). Data showing that AMPs influence the growth of tumor cells, exhibit direct cytotoxic activity towards cancer cells, function as a tumor suppressor gene or activate the adaptive immunity suggest that a dysregulation of AMPs may be associated with the development of cancer. There is no question that, with increasing resistance against conventional chemotherapy, novel anticancer agents are needed. It is interesting to speculate that natural AMP or synthetic derivatives can be used to develop novel strategies to fight cancer diseases and may represent a novel family of anticancer agents. However, future research is needed to employ the role of AMPs in cancer and to investigate their role as potential anticancer drugs.     

Antimicrobial peptides: current status and therapeutic potential

Antimicrobial peptides (AMPs) are effector molecules of the innate immune system. A variety of AMPs have been isolated from species of all kingdoms and are classified based on their structure and amino acid motifs. AMPs have a broad antimicrobial spectrum and lyse microbial cells by interaction with biomembranes. Besides their direct antimicrobial function, they have multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cell proliferation, immune induction, wound healing, cytokine release, chemotaxis and protease-antiprotease balance. AMPs qualify as prototypes of innovative drugs that may be used as antimicrobials, anti-lipopolysaccharide drugs or modifiers of inflammation. Several strategies have been followed to identify lead candidates for drug development, to modify the peptides' structures, and to produce sufficient amounts for pre-clinical and clinical studies. This review summarises the current knowledge about the basic and applied biology of AMPs.     

抗菌肽抗菌机制及与抗生素协同作用的研究进展

抗菌肽(antimicrobial peptides, AMPs)是一种新型抗生素，对多种细菌，多重耐药细菌均具有抗菌活性。然而，其副作用也是制约抗菌肽研发的主要障碍。研究者使用模式细胞膜，揭示抗菌肽与细胞膜之间的作用方式，开展抗菌肽开发和筛选研究。另外，研究者还将抗菌肽与常规抗生素联合使用，可以协同提高抗菌效果。研究初步揭示了AMPs和常规抗生素之间协同作用的机制。本综述探讨了模式细胞膜在AMPs发现筛选中的应用，及AMPs和常规抗生素之间联合用药的研发现状。     

Antimicrobial peptides: premises and promises

Antimicrobial peptides (AMPs) are an important component of the natural defences of most living organisms against invading pathogens. These are relatively small (<10 kDa), cationic and amphipathic peptides of variable length, sequence and structure. During the past two decades several AMPs have been isolated from a wide variety of animals, both vertebrates and invertebrates, and plants as well as from bacteria and fungi. Most of these peptides are obtained from different sources like macrophages, neutrophils, epithelial cells, haemocytes, fat body, reproductive tract, etc. These peptides exhibit broad-spectrum activity against a wide range of microorganisms including Gram-positive and Gram-negative bacteria, protozoa, yeast, fungi and viruses. A few peptides have also been found to be cytotoxic to sperm and tumour cells. AMPs are classified based on the three dimensional structural studies carried out with the help of NMR. The peptides are broadly classified into five major groups namely (a) peptides that form -helical structures, (b) peptides rich in cysteine residues, (c) peptides that form β-sheet, (d) peptides rich in regular amino acids namely histatin, arginine and proline and (e) peptides composed of rare and modified amino acids. Most of these peptides are believed to act by disrupting the plasma membrane leading to the lysis of the cell. AMPs have been found to be excellent candidates for developing novel antimicrobial agents and a few of these peptides show antimicrobial activity against pathogens causing sexually transmitted infection (STI), including HIV/HSV. Peptides, namely magainin and nisin have been shown to demonstrate contraceptive properties in vitro and in vivo. A few peptides have already entered clinical trials for the treatment of impetigo, diabetic foot ulcers and gastric helicobacter infections. In this review, we discuss the source, structures and mode of action with special reference to therapeutic considerations of various AMPs.     

Role of positively charged residues on the polar and non‐polar faces of amphipathic α‐helical antimicrobial peptides on specificity and selectivity for Gram‐negative pathogens

We have designed de novo and synthesized eight 26‐residue all D‐conformation amphipathic α‐helical cationic antimicrobial peptides (AMPs), four with “specificity determinants” which provide specificity for prokaryotic cells over eukaryotic cells and four AMPs without specificity determinants. The eight AMPs contain six positively charged Lys residues on the polar face in four different arrangements to understand the role of these residues have on antimicrobial activity against 14 Acinetobacter baumannii strains, seven of which were resistant to polymyxin B and colistin; six diverse Pseudomonas aeruginosa strains and 17 Staphylococcus aureus strains, nine of which were methicillin‐sensitive, and eight of which were methicillin‐resistant. The four AMPs without specificity determinants are extremely hemolytic. In contrast, the four AMPs with specificity determinants had dramatic improvements in therapeutic indices showing the importance of specificity determinants in removing eukaryotic cell toxicity. The specificity determinants combined with the location of positively charged residues on the polar face provide Gram‐negative pathogen selectivity between A. baumannii and S. aureus. Specificity determinants maintain excellent antimicrobial activity in the presence of human sera, whereas the AMPs without specificity determinants were inactive. This study clearly shows the potential of amphipathic α‐helical AMPs with specificity determinants as therapeutics to replace existing antibiotics.     

Potential roles of histones in host defense as antimicrobial agents

Antimicrobial peptides (AMPs), which are widely distributed in various organisms, comprise part of the host innate defense system to kill or damage bacterial and fungal pathogens. Amphibian skin is known to produce various AMPs, and is used as a source material in attempts to identify novel therapeutic AMPs. More than one hundred frog AMPs have been identified to date. In our previous study, we isolated histone H2B with antibacterial properties from the skin of the Schlegel's green tree frog Rhacophorus schlegelii. Although antimicrobial histone H2B has not been obtained from the skin of any species other than R. schlegelii, histones and histone-derived fragments with antimicrobial activities have been found in some specific cells of a diverse range of organisms from shrimps to humans. At least a portion of these fragments are known to be produced from "precursor histones" via specific cleavage by endogenous proteases. These antimicrobial histones and the fragments that act as physiological barriers of cells have a variety of antimicrobial actions and functions, including bacterial cell membrane permeabilization, penetration into the membrane followed by binding to bacterial DNA and/or RNA, binding to bacterial lipopolysaccharide (LPS) in the membrane, neutralizing the toxicity of bacterial LPS, and entrapping pathogens as a component of neutrophil extracellular traps (NETs). This review discusses the literature regarding the isolation, antimicrobial properties, and modes of action of antimicrobial histones and fragmented histones along with a brief introduction of typical amphibian skin AMPs.     

The use of technetium-99m radiolabeled human antimicrobial peptides for infection specific imaging

Bacterial resistance to conventional antibiotics poses a challenge medicine to search for alternatives. Cationic antimicrobial peptides (AMPs) are promising for the development of a new class of antibiotics. This review focuses on the use of technetium-99m labeled synthetic AMPs, derived from human natural cationic AMPs, for target-delivery to and in vivo detection of infection sites caused by (drug-resistant) micro-organisms. The scintigraphic approach has proven to be a reliable method for evaluating AMPs in pharmacological studies and for optimizing target-delivery of radiolabeled AMPs to pathological sites in animals and humans. In addition, the effect of alterations in amphipathicity, amino acid substitution, and dimerization on the biological performance of AMPs is reported. Radiolabeled AMPs offer good perspectives for diagnosis of infections, for monitoring therapy, and, most importantly, for the ability to discriminate between infections and sterile inflammatory processes.     

Current state of a dual behaviour of antimicrobial peptides—Therapeutic agents and promising delivery vectors

Micro‐organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti‐inflammatory, wound‐healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide‐based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields.     

两栖类皮肤抗菌肽的分离纯化与抗菌活性检测技术

两栖类皮肤抗菌肽由于具有广谱、高效的抗菌活性,且不引起微生物耐药性等特点,已成为目前开发新型抗菌药物的理想材料。文章概述了两栖类抗菌肽的主要特点及其分离纯化和抗菌活性检测的主要方法,并对这些技术的原理、方法及其近年来在抗菌肽研究中的进展进行了介绍。同时本文还比较了各种方法的优缺点,对当前研究中所存在的一些问题进行了初步的探讨,以期为两栖类抗菌肽的应用提供理论依据。