肠道菌群代谢物检测新技术的应用及其研究进展

随着微生物在人体内的作用越来越受到关注,肠道菌群的作用已成为近年来研究的热门领域之一。综述肠道菌群的分布、多种分子生物学技术(如质谱、聚合酶链式反应、基因芯片等)在肠道菌群作用研究方面的应用资料,并分析了其研究与展望。     

阿德福韦与DNA作用的盐效应及热力学作用分析

目的研究阿德福韦与小牛胸腺DNA结合作用的盐效应及热力学作用。方法采用荧光光谱法、热力学理论研究阿德福韦与DNA的相互作用。结果证实了阿德福韦是通过嵌插作用模式与DNA发生了相互作用。结论阿德福韦与DNA之间存在嵌插作用模式,其相互作用力为静电作用。     

蛋白质组学技术在硒化合物作用机制研究中的应用

硒是人体中非常重要的微量元素,其化合物的存在形式是多种多样的。硒具有很强的抗氧化、防癌抑癌作用,其作用是通过多种机制产生的。蛋白质组学的产生与发展为在蛋白质水平上探索硒化合物对机体的作用模式、功能机理、调节调控方式提供了技术支持,从而为病理研究、药物筛选、新陈代谢途径研究等提供依据。     

芍药苷在治疗肝癌中作用及其机制的研究进展

芍药苷是中药白芍的主要有效成分,许多研究发现其具有缓解炎症、抗风湿和免疫调节等药理作用。除此之外,近年来对芍药苷保肝作用的研究逐渐增多。芍药苷不仅对肝炎、肝损伤和肝纤维化有保护作用,而且在抗肿瘤方面的作用也逐渐引起了人们的关注。其抗肝癌的作用机制主要与不同信号途径引起的细胞凋亡、阻止癌细胞增殖、侵袭、转移以及保护肝脏的功能有关。     

阿德福韦与DNA作用的盐效应及热力学作用分析

目的 研究阿德福韦与小牛胸腺DNA结合作用的盐效应及热力学作用.方法 采用荧光光谱法、热力学理论研究阿德福韦与DNA的相互作用.结果 证实了阿德福韦是通过嵌插作用模式与DNA发生了相互作用.结论 阿德福韦与DNA之间存在嵌插作用模式,其相互作用力为静电作用.     

多酚类化合物的药代动力学研究概况

综述多酚类化合物在生物体内吸收、分布、代谢和排泄的规律与特征,以期能为其药代动力学相关研究提供有价值的信息,从而促进多酚类化合物的研发。多酚类化合物在自然界中广泛分布,且具有良好的保健和治疗作用。药代动力学研究在揭示其在生物体内的有效物质形式、阐明其作用机制等方面具有重要作用。     

纳米载体材料毒理学效应及其作用机制研究进展

目的:为研究纳米载体材料的毒理学效应及其作用机制提供依据。方法:根据文献,综述了纳米载体材料在体内的毒性来源与作用机制、给药方式与纳米载药系统毒性的关系两方面的研究现状。结果:毒性主要来源包括其粒径、表面电荷及表面修饰等因素,毒性作用机制是由自由基的产生引发氧化应激所致;吸入、静脉注射、口服等给药方式均可能在体内产生毒性。结论:通过降低给药浓度、修饰载体表面基团等方式可有效控制和降低纳米载体材料的毒性作用,只有充分掌握其在体内的作用机制,为纳米载药系统安全评估工作提供科学依据,才可使其更安全地应用于人类。     

加强护理药理学改革,促进高级护理人才培养

药理学是研究药物与机体相互作用及作用规律的学科,其是以基础医学中的生理学、生物化学、病理学、病理生理学、微生物学、免疫性、分子生物学等为基础,为防治疾病、合理用药提供基本理论、基本知识和科学的思维方法,是基础医学与临床医学以及医学与药学的桥梁。而护理专业与临床医学及其他医学专业一样对,要求具备良好的药理学知识基础。护理药理学是药理学的一个新的分支,其在研究药物与机体相互作用的同时,渗入了护理工作在药物监测中的作用,强调了实施药效评价过程中的科学化、目标化护理。     

药食两用中药抗癌作用及其与归经的相关性研究

目的从药食两用中药抗癌的研究与应用角度探讨其与归经的关系,为药食两用中药在抗肿瘤天然药物研究与应用方面提供依据与参考。方法以《中国药典》2010年版收录的、2012年卫生部公布的药食同源品种共有87种药食两用中药作为研究对象,系统地总结了其性味归经、化学成分、药理作用,并从其抗癌的研究与应用角度探讨了其与归经的关系。结果药食两用中药在配合手术及放化疗诊治恶性肿瘤及其并发症的过程中常能发挥意想不到的良效。在中医归经理论的指导下用药,可以把药效部位和治疗病灶相联系,使祛邪扶正趋向于靶点。结论随着中药药理学、免疫学、细胞生物学、分子生物学等多学科研究方法和技术手段的发展,中药及其有效成分的抗肿瘤作用研究已成为世界性的研究热点,而若在使用药食两用中药进行肿瘤辅助治疗时,结合辨证施治的治疗理念,合理用药,会使其选择与应用更具可靠性和针对性,能够更好地发挥治疗作用。     

马钱子碱抗肿瘤及减毒增效的研究进展

马钱子碱是从马前科植物马钱子中提取的弱碱性吲哚型生物碱,是马钱子发挥作用的主要成分,其含量仅次于士的宁。研究表明马钱子碱具有抗肿瘤、镇痛抗炎、免疫调节等作用,同时对神经系统、心血管系统、骨骼系统等也有一定的药理作用。现代研究越来关注于马钱子碱的抗肿瘤作用,多数研究显示马钱子碱可通过诱导肿瘤细胞凋亡发挥抗肿瘤作用,但其机制尚不清楚,加之马钱子碱具有毒性,在一定程度上限制了它的使用与研究,但基于马钱子碱良好的抗肿瘤作用,其减毒增效也受到越来越多的关注。下面就马钱子碱的抗肿瘤及减毒增效作用做一综述。     

Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain

Acid-sensing ion channels (ASICs) are Na⁺-permeable ion channels activated by protons and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation. At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, ASIC5) are encoded by five genes (ASIC1-ASIC5). Functional ASICs assembled in the plasma membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple cellular processes. ASICs are widely but differentially expressed in the central and peripheral nervous systems. In the mammalian brain, a majority of neurons express at least one ASIC subunit. Several recent reviews have summarized findings of the role of ASICs in the peripheral nervous system, particularly in nociception and proprioception, and the structure-function relationship of ASICs. However, there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons co-released with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in some pathologies such as epilepsy, mood disorders and Alzheimer''s disease.     

The pharmacology and therapeutic potential of small molecule inhibitors of acid-sensing ion channels in stroke intervention

In the nervous system, a decrease in extracellular pH is a common feature of various physiological and pathological processes, including synaptic transmission, cerebral ischemia, epilepsy, brain trauma, and tissue inflammation. Acid-sensing ion channels (ASICs) are proton-gated cation channels that are distributed throughout the central and peripheral nervous systems. Following the recent identification of ASICs as critical acid-sensing extracellular proton receptors, growing evidence has suggested that the activation of ASICs plays important roles in physiological processes such as nociception, mechanosensation, synaptic plasticity, learning and memory. However, the over-activation of ASICs is also linked to adverse outcomes for certain pathological processes, such as brain ischemia and multiple sclerosis. Based on the well-demonstrated role of ASIC1a activation in acidosis-mediated brain injury, small molecule inhibitors of ASIC1a may represent novel therapeutic agents for the treatment of neurological disorders, such as stroke.     

酸敏感离子通道在缺血性脑损伤中的作用

综述近年来有关酸敏感离子通道在缺血性脑损伤中的作用研究,论及酸敏感离子通道在脑中的分布和作用、它的激活以及在缺血性脑损伤中的作用机制及与谷氨酸受体的协同作用.酸敏感离子通道是一类由胞外酸化所激活的阳离子通道,而缺血性脑损伤正是由其引起胞内Ca^2＋超载所致,因此抑制其激活可以对抗缺血性脑损伤,为神经系统缺血性损伤的保护及药物治疗研究提供了新思路.     

酸敏感离子通道在非神经组织中的功能研究

酸敏感离子通道(ASICs)是一类由细胞外酸化所激活的阳离子通道,属于钠通道超家族的新成员。近来发现,ASICs不但在神经系统具有重要的生物学功能,对神经系统以外的组织(如:味蕾、心血管、骨等)的生理和病理过程中也具有重要的作用。该文对有关ASICs在神经以外其他组织中研究的最新进展作一综述,以增进对ASICs生物学功能和病理作用的了解。     

Physiological and pathological functions of acid-sensing ion channels in the central nervous system

Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain ischemia, multiple sclerosis, epileptic seizures, and malignant glioma. Thus, targeting these channels may lead to novel therapeutic interventions for neurological disorders. The goal of this review is to provide an update on recent advances in our understanding of the functions of ASICs in the CNS.     

Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases

A significant drop of tissue pH or acidosis is a common feature of acute neurological conditions such as ischemic stroke, brain trauma, and epileptic seizures. Acid-sensing ion channels, or ASICs, are proton-gated cation channels widely expressed in peripheral sensory neurons and in the neurons of the central nervous system. Recent studies have demonstrated that activation of these channels by protons plays an important role in a variety of physiological and pathological processes such as nociception, mechanosensation, synaptic plasticity, and acidosis-mediated neuronal injury. This review provides an overview of the recent advance in electrophysiological, pharmacological characterization of ASICs, and their role in neurological diseases. Therapeutic potential of current available ASIC inhibitors is discussed.     

酸敏感离子通道抑制剂的研究进展

酸敏感离子通道(ASICs)是一类由胞外H 激活的阳离子通道。已发现的6个ASICs亚基在触觉、痛觉、酸味觉以及学习记忆中有重要的生理作用,同时,它们参与某些病理反应,可以被神经肽、温度、金属离子以及缺血诱导产生的一些活性物质所调控。基于其病理作用,ASICs抑制剂的研发成为药物化学研究的热点之一。本文综述了近年来对ASICs的结构、生理和病理作用及几类ASICs抑制剂的最新研究进展,并进行了展望。     

Diarylamidines: High potency inhibitors of acid-sensing ion channels

Acid-sensing ion channels (ASICs) are proton-gated cation channels that are predominantly expressed in the nervous system. ASICs are involved in a number of neurological diseases such as pain, ischemic stroke and multiple sclerosis but limited tools are available to target these channels and provide probes for their physiological functions. Here we report that the anti-protozoal diarylamidines, 4′,6-diamidino-2-phenylindole (DAPI), diminazene, hydroxystilbamidine (HSB) and pentamidine potently inhibit ASIC currents in primary cultured hippocampal neurons with apparent affinities of 2.8 μM, 0.3 μM, 1.5 μM and 38 μM, respectively. These four compounds (100 μM) failed to block ENaC channels expressed in oocytes. Sub-maximal concentrations of diminazene also strongly accelerated desensitization of ASIC currents in hippocampal neurons. Diminazene blocked ASIC1a, -1b -2a, and -3 currents expressed in CHO cells with a rank order of potency 1b > 3 > 2a ≥ 1a. Patchdock computational analysis suggested a binding site of diarylamidines on ASICs. This study indicates diarylamidines constitute a novel class of non-amiloride ASIC blockers and suggests that diarylamidines may be developed as therapeutic agents in treatment of ASIC-involved diseases.     

ASICs——治疗神经系统相关疾病药物作用的新靶点

酸敏感离子通道（Acid sensing ion channels，ASICs）是一种可以被H+激活的质子门控阳离子通道。近年来研究发现，ASICs参与癫痫、炎症性疼痛、缺血性脑损伤等神经系统相关疾病的病理过程，它被认为是治疗神经系统相关疾病药物作用的一个新靶点。本文主要综述ASICs在神经系统相关疾病中的调节作用，以及ASICs相关药物的最新研究进展。     

Current perspectives on acid-sensing ion channels: new advances and therapeutic implications

Acid-sensing ion channels (ASICs) form a family of voltage-independent cation channels that predominantly conduct Na+ ions, and were identified at the molecular level a little more than a decade ago. ASICs are activated by extracellular acidification within the physiological range, and they form effective proton sensors in both central and peripheral sensory neurons. A combination of genetic and pharmacologic approaches has revealed their implication in an increasing number of physiological and pathophysiological processes--most of them associated with extracellular pH fluctuations, ranging from synaptic plasticity, learning, memory, fear, depression, seizure termination and neuronal degeneration to nociception and mechanosensation. ASICs, therefore, emerge as new potential therapeutic targets in the management of psychiatric disorders, stroke, neurodegenerative diseases and pain.