氧化型低密度脂蛋白:致动脉粥样硬化和抗动脉粥样硬化的双重作用

研究证明,氧化型低密度脂蛋白(oxLDL),而不是低密度脂蛋白,是致动脉粥样硬化的独立危险因素.oxLDL主要通过巨噬细胞上的清道夫受体摄入oxLDL,引起血管壁泡沫细胞的堆积和脂纹的形成;oxLDL还改变了内皮细胞、平滑肌细胞、血小板的多种功能,使之释放多种致炎细胞因子,促进了炎症细胞的趋化和聚集.但最近有报道认为,口服免疫耐量的oxLDL可弱化早期和晚期动脉粥样硬化.因此,oxLDL不仅能导致动脉粥样硬化,在某些情况下,还具有抗动脉粥样硬化的作用.本文从辩证法的角度出发,系统的阐述oxLDL的这一双重作用.     

氧化应激与动脉粥样硬化

活性氧是细胞内多种氧化还原反应的正常代谢产物,当活性氧的生成速率大于清除时,过多的活性氧会直接损伤细胞,还可通过信号转导系统引发一系列病理生理过程.各种氧化物前体可刺激血管细胞产生活性氧,加速动脉粥样硬化的形成和发展.他汀类、普罗布考等药物是目前最有希望的治疗冠状动脉粥样硬化性心脏病的抗氧化药物.     

血管平滑肌细胞在动脉粥样硬化发生中的哲学思维

随着对血管平滑肌细胞增殖在动脉粥样硬化中研究的不断深入,逐步意识到细胞凋亡的存在及其相互之间的矛盾关系,对动脉粥样硬化的认识亦由从形态结构和生化组成等描述病变,发展为在细胞乃至分子基因水平上的深入研究,发现血管平滑肌细胞的增殖和凋亡在动脉粥样硬化形成过程中起重要作用。从哲学角度探讨血管平滑肌细胞在动脉粥样硬化发生中的作用,有助于科学的发现疾病的本质。     

高密度脂蛋白在动脉粥样硬化发病中的双重作用

生理状态的高密度脂蛋白（high density lipoprotein,HDL）被普遍认为具有抗动脉粥样硬化功效,是冠心病的重要保护因子。然而,在某些病理状态下,HDL的抗动脉粥样硬化功能受损,甚至逆转产生致动脉粥样硬化作用,药物干预又可改善HDL的抗动脉粥样硬化功能。用矛盾的哲学规律认识高密度脂蛋白与动脉粥样硬化的关系,并在实际工作中抓住主要矛盾,就能更有成效地开展对HDL研究。     

白介素-1家族在动脉粥样硬化中的作用

动脉粥样硬化(AS)是一种慢性炎症性疾病。促炎细胞、促炎因子以及抗炎细胞、抗炎因子在此过程中发挥了重要作用,双方相互抑制,特定环境可相互促进,构成了一个复杂的炎症网络系统。平衡打破则表现为促炎活性升高和抑炎活性降低,可促进斑块的进展和不稳定,导致心血管事件。近年来白细胞介素(IL)-1家族在AS过程中的作用受到重视。依据其在AS进程中的作用,将其分为促AS家族,抗AS家族以及未归类成员。     

血红素氧合酶-1与动脉粥样硬化和高血压的关系

血红素氧合酶-1（HO-1）是血红素分解的起始酶和限速酶,它分解血红素最终生成胆红素、一氧化碳和铁.这三种产物通过抗炎症损伤、抗氧化应激、抗细胞增殖、抗细胞凋亡、抑制血小板聚集、调节血管张力及细胞内信号传递等途径对心血管系统起着重要的保护作用.研究显示,HO的诱导剂及多种能降低心血管病风险的药物能诱导 HO-1表达增加,从而起到抗动脉粥样硬化的发生发展及调节血压的作用.因此开发临床可应用的HO诱导剂,甚至开发HO的基因治疗方法是目前研究的方向.     

免疫反应影响动脉粥样硬化进程的两面性

大量研究表明,动脉粥样硬化的发生和发展过程中,能观察到许多免疫反应。然而,免疫反应对动脉粥样硬化的作用却呈现为两面性;免疫系统的激活可加速动脉粥样硬化的形成和发展,也可表现出抗动脉粥样硬化功效。所以,适当的免疫调节干预,有望成为动脉粥样硬化的预防及治疗的新途径。     

赖氨酰氧化酶在动脉粥样硬化中的作用

赖氨酰氧化酶(lysyl oxidase,LOX)是一种铜依赖性氨基氧化酶,在多个组织器官中均有表达,能参与催化细胞外基质(extracellular matrix,ECM)中胶原和弹性纤维的赖氨酸残基交联,以维持细胞外基质的结构和功能正常。新近研究发现LOX与动脉粥样硬化亦有紧密关系。本文就LOX在动脉粥样硬化发生、发展过程中的联系作一综述。     

免疫反应影响动脉粥样硬化进程的两面性

大量研究表明,动脉粥样硬化的发生和发展过程中,能观察到许多免疫反应.然而,免疫反应对动脉粥样硬化的作用却呈现为两面性:免疫系统的激活可加速动脉粥样硬化的形成和发展,也可表现出抗动脉粥样硬化功效.所以,适当的免疫调节干预,有望成为动脉粥样硬化的预防及治疗的新途径.     

赖氨酰氧化酶在动脉粥样硬化中的作用

赖氨酰氧化酶(lysyl oxidase,LOX)是一种铜依赖性氨基氧化酶,在多个组织器官中均有表达,能参与催化细胞外基质(extracellular matrix,ECM)中胶原和弹性纤维的赖氨酸残基交联,以维持细胞外基质的结构和功能正常.新近研究发现LOX与动脉粥样硬化亦有紧密关系.本文就LOX在动脉粥样硬化发生、发展过程中的联系作一综述.     

热休克蛋白7O在动脉粥样硬化发病中的双重作用

大多研究表明,热休克蛋白70通过抗凋亡、抗氧化及抗炎症反应而在动脉粥样硬化发病中起保护作用。但亦有研究表明,热休克蛋白70通过促凋亡、促进炎症反应而在动脉粥样硬化的发生发展中起促进作用。说明热休克蛋白70在动脉粥样硬化发病中有双重作用,进行基础研究和临床干预时应考虑到其双面性。     

Science,atherosclerosis and the “age of unreason”: A review

Research in atherosclerosis has been dominated by the lipid hypothesis. The pathology of both the cholesterol-fed animal and of familial hypercholesterolemia has been misrepresented. The vascular lesions of these disorders are not atherosclerotic but manifestations of fat storage. There has been undue faith in the epidemiology of coronary heart disease and atherosclerosis. Fundamental defects in the epidemiological approach to the cause of atherosclerosis include: (1) misuse of cause and risk factors; (2) misuse of coronary heart disease as an imprecise and inappropriate surrogate endpoint in clinical and mortality studies; (3) use of fallacious monocausal death certificates and mortality rates; (4) assumed causal role of risk factors; (5) use of fallacious dietary data; (6) ecological fallacies; (7) nonspecificity of statistical correlations and selection bias; (8) failure to take note of inconsistencies; (9) inappropriate use of the blood cholesterol level as a surrogate of atherosclerosis (substitution game) without demonstration of any such effect on arteries; and (10) misplaced faith in pathological and experimental corroborative evidence. The epidemiology of atherosclerosis is based on unscientific methodology and the lipid hypothesis as currently envisaged is invalid. There is need to review the cholesterol-lowering campaign especially for normolipidemic subjects.     

中药及其提取物防治血管内皮细胞损伤的研究概况

血管内皮细胞衬覆于血管内膜表面,不仅是血液与血管壁之间的屏障,更是重要的内分泌和效应器官,内皮细胞损伤和功能障碍是动脉粥样硬化发生的启动步骤。近年来的研究表明,中药及其提取物对血管内皮细胞具有保护作用,因此对防治动脉粥样硬化相关疾病有重要的意义。     

血管平滑肌细胞——祸首还是福星

长期以来血管平滑肌细胞（ＶＳＭＣ）增殖被认为是动脉粥样硬化（ＡＳ）发生的绝对必要条件和介入性治疗后血管再狭窄（ＲＳ）的主要原因。许多搞ＲＳ的策略始终盯住抑制ＶＳＭＣ这一环节。然而这些方法在临床试验中很少邮到或基本没有益处。近来的临床和实验研究提示抑制ＶＳＭＣ可以导和脆弱的ＡＳ斑块不稳定而发生裂缝,破裂、血栓形成,引起心肌 死等急性冠状动脉症候群,因为ＶＳＭＣ合成释放的胶原等可以增加斑块的生物力学强     

C-反应蛋白与动脉粥样硬化——谁才是始作俑者

C-反应蛋白可用于监测冠心病患者病情变化、预测冠心病的预后以及预报健康人群冠心病的发病风险。最近的研究显示,C-反应蛋白可能是动脉粥样硬化的始动因子。药物干预可以通过降低C-反应蛋白发挥抗动脉粥样硬化作用。本文分析了C-反应蛋白与动脉粥样硬化的因果关系及其在临床工作中的重要意义。     

Potential and Foetal Value

The argument from potential has been hard to assess because the versions presented by friends and those presented by enemies have born very little resemblance to each other. I here try to improve this situation by attempting to bring both versions into enforced contact. To this end, I sketch a more detailed analysis of the modern concept of potential than any hitherto attempted. As one would expect, arguments from potential couched in terms of that notion are evident non‐starters. I then ask how the modern notion of potential needs to be supplemented in order to produce a more convincing argument. I then enquire whether the supplementations utilised in the most distinguished recent presentations of the argument have anything better than an ad hoc role to play in contemporary metaphysics. I conclude that the rehabilitation of the argument is unlikely; in any event, the onus of proof seems to be on the friend of that argument to show that it is uncontrived. Finally, I argue that the (modern) notion of potential has an important role to play in any plausible account of foetal value.     

Taking the Perceptual Analogy Seriously

This paper offers a qualified defense of a historically popular view that I call sentimental perceptualism. At a first pass, sentimental perceptualism says that emotions play a role in grounding evaluative knowledge analogous to the role perceptions play in grounding empirical knowledge. Recently, András Szigeti and Michael Brady have independently developed an important set of objections to this theory. The objections have a common structure: they begin by conceding that emotions have some important epistemic role to play, but then go on to argue that understanding how emotions play that role means that there must be some alternative, emotion-independent route to obtaining knowledge of value. If there has to be such an emotion-independent route, then the perceptual analogy breaks down in a significant way. In this paper, I argue that the right ways for sentimental perceptualists to respond to each of these objections are revealed by thinking through how analogous objections applied to perception and the empirical domain would be answered. Although Szigeti's and Brady's objections should not persuade sentimental perceptualists to give up their view, the objections do put important constraints on what a form of the view has to be like in order to do exciting metaethical work.     

FREE WILL AND LUCK

I present an account of how agents can know what they are doing when they intentionally execute object-oriented actions. When an agent executes an object-oriented intentional action, she uses perception in such a way that it can fulfil a justificatory role for her knowledge of her own action and it can fulfil this justificatory role without being inferentially linked to the cognitive states that it justifies. I argue for this proposal by meeting two challenges: in an agent's knowledge of her action perception can only play an enabling role (and no justificatory role) for the agent's knowledge and if perception has a justificatory role, then the agent's knowledge must be inferential.