NOD样受体蛋白3炎症小体在急性肺损伤/急性呼吸窘迫综合征中的作用机制研究进展

急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)是由多种非心源性肺内外因素引起的急性进行性呼吸衰竭,发病核心为过度放大或失控的炎症反应,目前没有特效的治疗药物.NOD样受体蛋白3(nucleotide-binding domain (NOD)-like receptor protein 3,NLRP3)炎症小体是细胞受到刺激时形成的多蛋白复合体,活化后导致细胞焦亡及IL-1β、IL-18等产生,在多种感染性、炎症性疾病中起重要作用.引起肺损伤的多种因素均可导致NLRP3炎症小体形成、活化,有研究提示,与ALI/ARDS中的过度炎症反应有关.因而深入研究NLRP3炎症小体在ALI/ARDS中的作用,对于进一步阐明ALI/ARDS的发病机制有重要意义,甚至有望成为治疗ALI/ARDS的新靶点.     

急性肺损伤发病机制的研究进展

目的急性肺损伤（ALI）是全身炎症反应综合征在肺部的表现，可进一步发展为急性呼吸窘迫综合征（ARDS），目前其发病机制及治疗取得了很大进展，但其发病率及病死率仍较高，其病死率高达30％-40％，随着失控的炎症反应引发多器官功能紊乱综合征理论的出现，对ALI的认识转向对炎症发生、调控的认识，参与炎症的炎症细胞和细胞因子则成为研究的热点，这些细胞和细胞因子，炎症介质构成了ALI炎症反应和免疫调节的“细胞网络”和“细胞因子网络”在其发病过程中发挥重要作用，本文对近年来的研究做一综述。     

模式识别受体PRRs在急性肺损伤/急性呼吸窘迫综合征发病机制中的作用研究进展

急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)是继发于肺内或全身的炎症反应过程,它由肺泡损伤导致并形成炎症性非心源性的肺水肿.模式识别受体(PRRs)参与先天免疫系统的激活,PRRs可以启动炎症信号级联反应,并释放促炎细胞因子.本综述对PRRs所包括的跨膜受体TLRs、胞质受体RLRs和NLRs以及下游炎症通路N...     

急性肺损伤/急性呼吸窘迫综合征与NF-κB信号转导关系的研究进展

急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)是临床上最常见的急危重症,其发病机制错综复杂,缺乏主动性治疗措施,病死率高。研究表明,核因子κB(NF-κB)为一种诱导型核转录因子,在ALI/ARDS发展过程中发挥极为广泛的功能,并与炎症反应具有密切的关系。现就ALI/ARDS、NF-κB信号转导通路及两者的关系作一简要的论述。     

ALI/ARDS抗炎治疗研究的策略与展望

急性肺损伤(acute lung injury, ALI)既是呼吸道重大疫病(如SARS、禽流感)的病理基础,也是全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)时最易出现的组织损伤[1].ALI进一步发展即为急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS).随着失控性的炎症反应(uncontrolled inflammatory response)引发多器官功能障碍综合征(multipile organs disfunction syndrome, MODS)学说的提出,人们对ALI／ARDS 认识转向对炎症发生、调控的认识,参与炎症反应的炎症细胞和细胞因子则成为研究的热点[2-5].     

肺血管内皮细胞分泌功能的改变与急性肺损伤/急性呼吸窘迫综合征

急性肺损伤(acute lung injury,ALI)/急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)是临床上常见的急危重症,病死率高达25%~45%,治疗上主要限于器官功能与全身支持治疗,尤其是呼吸支持治疗,“等待”肺损伤的缓解。在ARDS发病机制中肺血管内皮细胞(pulmonary vascular endothelial cell,PVEC)既是受损的主要靶细胞,更是活跃的炎症和效应细胞,血管内皮细胞(vascular endothelial cell,VEC)的激活和损伤程度与ARDS预后密切相关。本文将主要阐述ALI/ARDS发病机制中PVEC部分分泌功能的改变。     

干细胞旁分泌效应在ALI/ARDS治疗中的研究进展

急性肺损伤(acute lung injury,ALI)以及它的严重形式——急性呼吸窘迫综合征(acute respiratorydistress syndrome,ARDS)是危重病人发病和死亡的重要原因之一,最近2个世纪以来,死亡率仍在36%～44%左右。ALI/ARDS的病因众多,发病机制十分复杂,涉及的环节多,受损的靶细胞多,主要涉及的环节有:炎症反应失控、细胞损伤与修复、细胞凋     

肾上腺髓质素参与大鼠急性肺损伤的发病

急性肺损伤(acute lung injury,ALI)是指由不同原因引起的包括肺泡上皮、肺毛细血管内皮和肺间质的急性弥漫性损害,临床治疗困难。ALI发病机制十分复杂,近年研究发现,血管内皮细胞及相关因子在ALI发病中起着重要的作用。肾上腺髓质素(adrenomedullin,Adm)是一种新的血管     

ω-3多不饱和脂肪酸对急性肺损伤炎症反应及免疫功能影响的机制研究进展

烧(创)伤、吸入性损伤、严重感染以及休克等疾病过程中,机体内多种炎性介质的释放,引发炎性细胞向肺组织迁移,激活呈级联放大的炎症反应,常常可造成以肺毛细血管内皮细胞和肺泡上皮细胞损伤为主的急性肺损伤(ALI),严重者短时间内可迅速发展为急性呼吸窘迫综合征(ARDS),病死率极高。ω-3多不饱和脂肪酸(ω-3PUFA)作为药理性免疫营养素的重要组成部分,目前已经超越了以往单纯提供能量、恢复正氮平衡的范畴,发挥着调控机体炎症反应、免疫功能的全面作用,并逐渐演变为现代危重性肺损伤治疗的重要组成部分。因此,本文就ω-3PUFA对ALI炎症反应及免疫功能影响的机制作一综述,旨在为临床治疗ALI提供理论依据。     

胸腺基质淋巴细胞生成素促进纤维化并激活MRC-5细胞中的丝裂原活化蛋白激酶

正急性肺损伤(acute lung injury,ALI)是一种可以危及生命的低氧性呼吸紊乱发生率和死亡率极高。ALI通常表现为广泛炎症和肺纤维化,伴有促炎、促纤维化因子和胶原蛋白蓄积。胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)在炎症调控过程中发挥着重要作用,但其对肺纤维化和ALI的作用尚不清楚。Li等据此探讨TSLP在肺纤维化进程中发挥的     

Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury

Background  

Toll like receptors (TLRs) signaling pathways, including the adaptor protein Mal encoded by the TIRAP gene, play a central role in the development of acute lung injury (ALI). Recently, the TIRAP variants have been described association with susceptibility to inflammatory diseases. The aim of this study was to investigate whether genetic variants in TIRAP are associated with the development of ALI.     

Concise review: Mesenchymal stem cells for acute lung injury: role of paracrine soluble factors

Morbidity and mortality have declined only modestly in patients with clinical acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), despite extensive research into the pathophysiology. Current treatment remains primarily supportive with lung-protective ventilation and a fluid conservative strategy. Pharmacologic therapies that reduce the severity of lung injury in preclinical models have not yet been translated to effective clinical treatment options. Consequently, further research in translational therapies is needed. Cell-based therapy with mesenchymal stem cells (MSCs) is one attractive new therapeutic approach. MSCs have the capacity to secrete multiple paracrine factors that can regulate endothelial and epithelial permeability, decrease inflammation, enhance tissue repair, and inhibit bacterial growth. This review will focus on recent studies, which support the potential therapeutic use of MSCs in ALI/ARDS, with an emphasis on the role of paracrine soluble factors.     

CD40 plays a crucial role in lipopolysaccharide-induced acute lung injury

Activated alveolar macrophages (AMphi) are known to constitute a critical modulator of the lung inflammatory response through the production of various mediators. However, the role of activated AMphi in acute lung injury (ALI) and acute respiratory distress syndrome is less well known. To address this issue, we examined a lipopolysaccharide (LPS)-induced lung injury model for the role of activated AMphi in vivo, focusing on activation through CD40, which is one of the most important pathways for the activation of antigen-presenting cells. Without CD40, LPS-induced ALI was significantly reduced in its histological degree of injury and recruitment of neutrophils into the lung. In addition, the release in the lung of inflammatory mediators such as tumor necrosis factor-alpha, interleukin-1beta, macrophage inflammatory protein 2, or matrix metalloproteinase was significantly reduced in mice deficient in CD40 (CD40KO). To elucidate the mechanism of this attenuation of ALI in CD40KO mice, we studied the function of AMphi ex vivo. AMphi purified from CD40KO mice could not induce expression of inducible nitric oxide synthase (iNOS) by LPS, although iNOS in wild-type AMphi was induced by LPS independently of CD40-CD154 interaction. The loss of surface expression of CD40 was enough to interrupt the expression of iNOS in AMphi in response to LPS. Also based on the tissue nitrotyrosine staining, the reactive oxygen and nitrogen intermediates seemed to be reduced in tissue in CD40KO mice. These results indicated that activation of AMphi through CD40 might be involved not only in amplification by the interaction with CD154 but also in the development of ALI by CD40 itself, and that the functional blockade of CD40 would yield one of the targets for the treatment of LPS-induced ALI and acute respiratory distress syndrome.     

IL-27 is Elevated in Acute Lung Injury and Mediates Inflammation

Cytokines play a critical role in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here we investigated whether IL-27 was elevated in patients with ALI/ARDS and its potential clinical significance. Bronchoalveolar lavage (BAL) and serum samples were obtained from 58 ALI/ARDS patients, and 25 control healthy volunteers. IL-27 and other inflammatory mediators were measured in BAL and serum by ELISA. Besides, a mouse model of cecal ligation and puncture (CLP)-induced lung inflammation/injury was established, and serum, BAL fluid and tissues were collected for analyses in the presence or absence of IL-27 neutralizing antibodies. BAL IL-27 was found to be significantly higher in patients with ALI/ARDS than that in controls, particularly of pulmonary origin; serum IL-27 was also significantly higher. Increased IL-27 was associated with markers of inflammation, and correlated with disease severity of patients in ALI/ARDS. In a mouse model of CLP-induced lung inflammation/injury, elevated IL-27 levels were observed in the lung, serum, and BAL fluids. IL-27 neutralizing antibody treatment reduced pulmonary inflammation and lung injury and improved mouse survival in response to CLP. Therefore, IL-27 is a critical cytokine in ALI/ARDS and inhibition of IL-27 may open a promising approach for ALI/ARDS patients.     

慢性酗酒与急性肺损伤/急性呼吸窘迫综合征

急性肺损伤/急性呼吸窘迫综合征(acute lung injury/accute respiratory distress syndrome,ALI/ARDS)是在非心源性疾病过程中.     

Methoxyeugenol Protects Against Lung Inflammation and Suppresses Neutrophil Extracellular Trap Formation in an LPS-Induced Acute Lung Injury Model

Inflammation - Acute lung injury (ALI) is a life-threatening acute inflammatory disease with high rates of morbidity and mortality worldwide. 4-Allyl-2,6-dimethoxyphenol (methoxyeugenol), a...