慢性炎症与动脉粥样硬化关系的研究进展

动脉粥样硬化(atherosclerosis,AS)的发病机制非常复杂,对其研究经历了一个半世纪,直到1999年Ross提出"动脉粥样硬化是一种炎症性疾病",各种炎症细胞和炎症因子参与动脉粥样硬化的发生和发展过程。已有众多的基础和临床研究都证实炎症在AS中的重要作用,但仍需要对AS发生发展的深入研究,使我们更准确认识和有效的防治AS。本文就近年来慢性炎症与动脉粥样硬化关系的研究进展作一综述。     

炎症与动脉粥样硬化及冠状动脉疾病的关系

炎症在冠状动脉疾病和其他动脉粥样硬化性疾病中起着重要作用.在动脉粥样硬化早期病变处存在大量的免疫细胞,它们所分泌的一系列细胞因子加速病变的进程,激活炎症反应导致急性冠脉综合症的发生.动脉粥样硬化,是冠状动脉疾病的主要病因,是一种炎性疾病,炎症因子参与到免疫反应过程中,使得动脉壁处的病变得以发生、蔓延和活化.     

慢性炎症、自身免疫和动脉粥样硬化

动脉粥样硬化是一种炎症性疾病。在粥样斑块中存在许多免疫细胞,而且在不稳定斑块中尤为丰富。近年来对动脉粥样硬化中免疫细胞的聚集,分化和激活有了更深入的了解。流行病研究发现了多种与其相关的病毒和细菌感染。通过研究初步研究了几个自身性抗原,并提出了自身免疫假说。根据这些新的认识,提出了免疫调节和预防接种等心血管疾病的预防和治疗策略。这必将极大地提高对动脉粥样硬化的研究和防治水平。     

炎症与肿瘤的关系研究进展

炎症与肿瘤关系密切,慢性炎症与1/4以上癌症发生相关.炎症微环境中细胞因子,自由基,前列腺素,生长因子等炎性应答介质能诱导DNA甲基化,抑癌基因点突变和翻译后修饰等基因和表观学变化,引起维持正常细胞内环境稳定关健通路的改变并导致癌症的发生和演进;近年来,对炎症中microRNA和免疫应答相互作用的研究进一步加深了人们对炎症与肿瘤相关性的了解.本文就炎症与肿瘤的间的桥梁分子予以综述,鉴定这些关键细胞成分及相互通路特异性的改变能为炎症相关性肿瘤的早期诊断、预防和治疗提供分子靶标.     

炎症小体在动脉粥样硬化发生发展中的研究进展

炎症小体(inflammasome)是免疫细胞内由多种蛋白质所组成的复合体,属于胞浆型模式识别受体(pattern recognition receptor,PRR)。它作为固有免疫系统的重要组分在机体免疫反应和疾病发生过程中具有重要作用。近年来的研究表明炎症小体是炎症免疫反应的核心。由于能被多种类型的病原体或危险信号所激活,NLRP3(NOD样受体蛋白-3)炎症小体在多种疾病过程中,包括动脉粥样硬化症、家族性周期性自身炎症反应、阿尔海默茨病和2型糖尿病等都发挥了关键作用。因此,NLRP3(NOD样受体蛋白-3)炎症小体可能为各种炎症性疾病,包括动脉粥样硬化的治疗提供新的靶点。本文将对炎症小体在动脉粥样硬化发生发展中发挥的作用进行综述。     

维持性血液透析患者微炎症及氧化应激与动脉粥样硬化的关系

目的:探讨维持性血液透析患者微炎症及氧化应激状态与动脉粥样硬化的关系.方法:测定35例1年以上透析充分的维持性血液透析(maintenance hemodialysis,MHD)患者透析前血肌酐(Scr)、血尿酸(UA)、血糖(Glu)、血浆白蛋白(ALB)、甘油三酯(TG)、胆固醇(TC)、C反应蛋白(CRP)、IL-6、肿瘤坏死因子α(TIF-α)、血浆丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、血浆谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px).应用超声测定颈动脉中层厚度(IMT)及有无颈动脉斑块形成.结果:AS组CRP、IL-6及TNF-α明显高于非AS组,两组之间差异有显著性(P＜0.05);同时,AS组血清MDA水平显著高于非AS组,SOD和GSH-Px水平显著低于非AS组,两组差异有显著性(P＜0.05).而两组在年龄、性别构成、血压、血脂、血糖、血尿酸无统计学差异.结论:微炎症及氧化应激共同参与了MHD患者动脉粥样硬化的形成.     

不同脂肪组织与动脉粥样硬化关系的研究进展

动脉粥样硬化是一种复杂的心血管疾病,由动脉内部脂质代谢紊乱和炎症引起,目前仍是全球死亡的主要原因之一.而肥胖引起的脂肪组织功能障碍能够诱发血脂异常、激活血管炎症,促进动脉粥样硬化的发生.脂肪组织包括白色脂肪组织(white adipose tissue,WAT)、棕色脂肪组织(brown adipose tissue,...     

慢性炎症与甲状腺癌关系的研究进展

甲状腺癌是内分泌系统恶性肿瘤中最为常见的类型,其发病率约占90％,且仍有上升趋势。近年来,随着免疫学技术及分子生物学技术的快速发展和人类对甲状腺癌发病机制认识的不断深入,慢性炎症与甲状腺癌的相关性引起了大家的广泛关注。因此,本文就慢性炎症与甲状腺癌的最新研究进展进行综述。     

纤维蛋白（原）与动脉粥样硬化关系的研究进展

动脉粥样硬化是常见的血管病变,众多研究表明纤维蛋白(原)是动脉粥样硬化的独立危险因素.纤维蛋白(原)能够调节炎性细胞黏附和迁移,使血液处于高凝状态,刺激血管平滑肌细胞增殖和迁移.本文综述纤维蛋白(原)和动脉粥样硬化发病机制之间的关系.     

炎症促进大鼠动脉粥样硬化初期内皮功能病变机制研究

目的:观察炎症因素诱导大鼠动脉粥样硬化发病过程中对血管内皮细胞的影响。方法:实验分为单纯高脂对照组和炎症组,分别腹腔注射给予无菌医用液体石蜡和酵母多糖(Zym,20mg/kg,1次/3天)。所有大鼠均喂食含3%胆固醇的高脂饲料,共8周。透射电镜观察主动脉超微结构;应用定量PCR法测定腹主动脉组织中诱导型一氧化氮合酶(iNOS)mRNA、血管细胞粘附分子(VCAM)-1 mRNA、以及基质金属蛋白酶7(MMP7)mRNA的表达。结果:炎症组可见游走于内膜下层的平滑肌细胞和和吞噬脂质颗粒的单核细胞,单纯高脂对照组仅见内皮细胞损伤和退行性变,未见内膜下层形成泡沫细胞,AS样病变较炎症组轻。与对照组相比,炎症组动脉壁iNOS mRNA表达降低,VCAM-1 mRNA及MMP7 mRNA标大量显著升高。结论:炎症刺激能够损伤动脉血管内皮细胞,诱导炎症因子释放增加,促进动脉粥样硬化的发生。     

A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites

Chronic inflammation is a major driver of pathological tissue damage and a unifying characteristic of many chronic diseases in humans including neoplastic, autoimmune, and chronic inflammatory diseases. Emerging evidence implicates pathogen-induced chronic inflammation in the development and progression of chronic diseases with a wide variety of clinical manifestations. Due to the complex and multifactorial etiology of chronic disease, designing experiments for proof of causality and the establishment of mechanistic links is nearly impossible in humans. An advantage of using animal models is that both genetic and environmental factors that may influence the course of a particular disease can be controlled. Thus, designing relevant animal models of infection represents a key step in identifying host and pathogen specific mechanisms that contribute to chronic inflammation.Here we describe a mouse model of pathogen-induced chronic inflammation at local and systemic sites following infection with the oral pathogen Porphyromonas gingivalis, a bacterium closely associated with human periodontal disease. Oral infection of specific-pathogen free mice induces a local inflammatory response resulting in destruction of tooth supporting alveolar bone, a hallmark of periodontal disease. In an established mouse model of atherosclerosis, infection with P. gingivalis accelerates inflammatory plaque deposition within the aortic sinus and innominate artery, accompanied by activation of the vascular endothelium, an increased immune cell infiltrate, and elevated expression of inflammatory mediators within lesions. We detail methodologies for the assessment of inflammation at local and systemic sites. The use of transgenic mice and defined bacterial mutants makes this model particularly suitable for identifying both host and microbial factors involved in the initiation, progression, and outcome of disease. Additionally, the model can be used to screen for novel therapeutic strategies, including vaccination and pharmacological intervention.     

调节慢性炎症防治衰老相关疾病的研究进展

衰老是应激、损伤、感染、免疫反应衰退以及代谢障碍等综合作用积累的结果。细胞在衰老的过程中会分泌大量的炎性因子。相关研究表明,老年人的皮肤及粘膜对细菌、病毒感染、外伤等等方面的抵抗和防御能力明显低于青年人,炎性因子不断增多,加速细胞衰老。由此可见,控制慢性炎症可能是干预衰老的有效途径。生物活性透明质酸可能通过诱导防卫素分泌和与CD44/TLR4受体结合,抑制细菌生长和炎症进展,从而发挥抗衰老作用。本文对有关慢性炎症和衰老之间的关系的研究进行综述,探讨生物活性透明质酸对慢性炎症的调节作用及其抗衰老机制。     

Effect of Shiftwork on Systemic Markers of Inflammation

Shiftwork is associated with an increased risk of cardiovascular diseases, but the possible role of inflammation in this relationship is not well known. We tested the hypothesis that shiftwork would be associated with higher levels of C-reactive protein (CRP) and increased leukocyte count. We analyzed the cross-sectional associations between work arrangements and low-grade inflammation in 1877 airline-company employees separately for men (n?=?1037) and women (n?=?840). The participants were classified into five categories according to their work schedule: day workers who have not worked in shifts (referent group), former shiftworkers, 2-shift workers, 3-shift workers, and in-flight workers. In models adjusted for age and recent infectious diseases, CRP levels were higher among male 3-shift workers (p = .002) and marginally higher in male 2-shift workers (p = .076). In addition, leukocyte count was higher in 2-shift (p = .005) and 3-shift (p = .021) working men. In women, CRP level was higher in 2-shift workers (p = .028), whereas leukocyte count was lower in flight workers (p = .005). Any separate adjustment additionally for smoking, education, alcohol consumption, physical activity, and obesity did not substantially affect the results of 2- and 3-shift work. In the fully adjusted model, only the association between 3-shift work and CRP in men (p = .021) and 2-shift work and leukocyte count in men (p = .020) and leukocyte count in 3-shift-working women (p = .044) were significant. Our results suggest that 2- and 3-shift work is associated with increased systemic inflammation and the relationship is relatively independent of the considered risk factors of cardiovascular disease. (Author correspondence: Sampsa.Puttonen@ttl.fi)     

氧化三甲胺与动脉粥样硬化关系的研究进展

动脉粥样硬化(atherosclerosis,AS)所致心脑血管疾病是一类严重危害人类健康的疾病.近年来研究发现,肠道菌群代谢物氧化三甲胺(trimethylamine oxide,TMAO)在AS发病机制中起到重要作用:抑制胆固醇逆向转运、上调清道夫受体的表达水平、促进泡沫细胞形成、缩小胆汁酸池、增强血小板反应性、增...     

肥胖与慢性炎症的研究进展

肥胖常伴随着一系列代谢综合征的发生,肥胖引起的慢性炎症因为与各种代谢综合征的密切联系而成为目前的研究热点。慢性炎症的发生很复杂,涉及多个组织、器官和系统,并且炎症的发生会反过来影响组织的功能。目前针对慢性炎症发生机制的研究结果显示脂肪因子和免疫系统、内质网应激、细胞自噬作用以及内毒素的作用等形成的信号网络参与了慢性炎症的触发和发展。本文就慢性炎症与肥胖关联的几种可能发生机制的最新研究进展作一简要综述。     

青藤碱对慢性非细菌性大鼠前列腺炎大鼠炎症反应及P38Mapk信号通路的影响

目的：观察青藤碱对慢性非细菌性大鼠前列腺炎大鼠炎症反应及P38Mapk信号通路的影响。方法：将SD大鼠随机分为对照组、青藤碱高、低剂量组。对照组组给予生理盐水灌胃,青藤碱低、中、高剂量组分别给予青藤碱40,80、160mg／kg灌胃,28天后处死。realtimeRT-PCR法和westernblot法检测肿瘤组织中TNF-、IL-6rnR_NA和TNF-、IL-6、P—P38MAPK蛋白的表达。结果：青藤碱能明显降低慢性非细菌性大鼠前列腺炎大鼠前5,1腺组织中TNF-、IL-6mRNA和TNF-、IL-6、p-P38MAPK蛋白的表达。结论：青藤碱能抑制慢性非细菌性大鼠前列腺炎大鼠前列腺炎症反应,其机制可能与抑制P38MAP信号通路有关。     

FGF21类似物治疗动脉粥样硬化机制研究进展

动脉粥样硬化是冠心病、脑梗死、外周血管病的主要诱因,近年来发病率越来越高,严重威胁着人类生命健康。脂质代谢障碍是动脉粥样硬化的病理基础。成纤维细胞生长因子21(FGF21)是FGF家族的一种内分泌因子,它能够增加葡萄糖的摄取,调节脂质代谢,并使代谢活跃的器官（如肝脏和脂肪组织）中胰岛素反应敏感。FGF21水平与动脉粥样硬化的发生率和严重程度密切相关。然而,FGF21原型在血浆的半衰期短、体外易聚集,严重限制了其临床应用。近年来,对FGF21类似物的研究取得了突破性进展。综述了FGF21的生理作用,并讨论了基于FGF21类似物治疗动脉粥样硬化的主要突破和局限性,为FGF21蛋白类新药的开发提供了理论依据。