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。     

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].     

急性呼吸窘迫综合征的药物治疗

急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)的防治是多途径、综合性的救治过程.目前尚无治疗急性肺损伤(acute lung injury,ALI)/ARDS的特效药物,对其有缓解作用的药物主要针对其的急性渗出期、炎症反应或氧化损伤以及纤维增生期.联合多种药理因素...     

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.     

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.     

急性肺损伤/急性呼吸窘迫综合征相关微RNA研究进展

微RNA(miRNA)是一组高度保守的长度约22个核苷酸的非编码RNA,通过靶定相应的互补序列导致mRNA的沉默或者抑制翻译以调节基因和蛋白的表达。急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)的发病机制错综复杂,涉及失控性炎症反应、细胞凋亡及肺泡液体清除异常等多个层面,而且各个层面相互影响形成复杂的细胞网络和细胞因子网络,其通过不同的信号转导通路调控机体炎症反应。ALI发病过程中miRNA表达异常,miRNA可通过与靶mRNA部分结合在转录和转录后水平调节靶基因表达,参与ALI的整个发病过程。本文总结了国内外ALI发病过程中相关miRNA的研究进展,旨在寻找和验证miRNA在ALI炎症激活和信号转导途径中的作用,为ALI的诊疗提供新靶点。     

NF-κB与重症急性胰腺炎肺损伤关系的研究进展

重症急性胰腺炎(severe acute pancreatitis,SAP)是指急性胰腺炎(acte pancreatitis,AP)伴有脏器功能障碍,或出现坏死、脓肿或假性囊肿等局部并发症,或二者兼有。占急性胰腺炎发病的5%~16%。病情严重,并发症发生率高,病死率高达20%~30%,病程长者可达数月[1]。急性肺损伤(acutelung injury,ALI)是SAP最常见而严重的并发症,是肺炎症和肺微血管通透性增加的急性、进行性缺氧性呼吸衰竭,其最终阶段即为急性呼吸窘迫综合(a-cute respiratory distress syndrome,ARDS)。近年来许多研究证实与SAP病程中肺内炎性细胞过度激活和凋亡延迟,肺组…     

急诊肺炎患者发生急性肺损伤/急性呼吸窘迫综合征危险因素分析

目的探讨急诊肺炎患者发生急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)的早期危险因素。方法回顾性分析中国医科大学附属第一医院急诊科收治的100例肺炎患者,其中男性62例,女性38例;年龄49~79岁,平均年龄62岁。观察72h,发展至ALI/ARDS为ALI/ARDS组,未发展至ALI/ARDS的分为单纯肺炎组。收集两组患者的年龄、性别、生命体征、初始所需吸氧浓度及初诊的实验室检查(白细胞、血小板计数、血清白蛋白、尿素氮、丙氨酸氨基转移酶)指标,对各项因素进行单因素分析,单因素分析有显著意义的变量行二项分类的Logistic回归分析。结果 100例患者35例发展为ALI/ARDS,65例未发展为ALI/ARDS。单因素分析结果显示,患者是否发展为ALI/ARDS与年龄、性别、体温、呼吸频率、休克、白细胞计数、尿素氮等比较,差异无统计学意义(P0.05);初始所需吸氧浓度(维持血氧饱和度≥90%)、改良后的快速急诊内科评分(REMS)、低蛋白血症与发展为ALI/ARDS差异有统计学意义(P0.05)。二项分类的Logistic回归分析显示,仅吸氧浓度、改良后的REMS评分是发展为ALI/ARDS的独立危险因素。其中吸氧浓度2 L/min的灵敏度为77.1%,特异度为86.2%;改良后的REMS≥7发生ALI/ARDS灵敏度为74.3%,特异度为72.3%。结论初始吸氧浓度及改良后的REMS评分与ALI/ARDS的发生存在正相关,初始吸氧浓度2 L/min和/或改良后的REMS≥7的肺炎患者应予以重视,是ALI/ARDS的高危患者,争取做到早期诊治。     

凝血和纤溶失衡在急性肺损伤中的作用

急性肺损伤(acute lung injury,ALI),以肺泡上皮细胞和血管内皮屏障损伤、急性炎症反应、富含蛋白的肺水肿为特征,是一种临床常见的危重病症,可进一步发展为急性呼吸窘迫综合症(acute respiratory distress syndrome,ARDS).     

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。     

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.     

Toll 样受体信号转导通路与急性肺损伤的研究进展

急性肺损伤(ALI)是由感染性和非感染性的炎症刺激因子启动的细胞内“瀑布式”反应所产生的,是一种具有高发病率和死亡率的急性炎症性疾病,其进一步发展将演变为急性呼吸窘迫综合征(ARDS)。ALI作为一种复杂的临床综合征,发病率和病死率很高,目前发病机制仍不完全明确,大量研究表明细胞因子的过度表达及其相互作用是发生ALI的根本原因。Toll样受体(TLRs)是一类在先天免疫系统中起重要作用并参与炎症过程的跨膜蛋白,可识别外源性病原体或细胞损伤。近年来研究发现,TLRs在调节ALI后的炎症和修复机制方面扮演着重要的角色,是一个潜在的治疗靶点。本文将就TLRs在急性肺损伤中的研究进展作一综述。     

Association between insertion/deletion polymorphism in angiotensin-converting enzyme gene and acute lung injury/acute respiratory distress syndrome: a meta-analysis

ABSTRACT: BACKGROUND: A previous meta-analysis reported a positive association between an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) and the risk of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Here, we updated this meta-analysis and additionally assessed the association of this polymorphism with ALI/ARDS mortality. METHODS: We searched electronic databases through October 2011 for the terms "angiotensin-converting enzyme gene", "acute lung injury", and "acute respiratory distress syndrome," and reviewed all studies that reported the relationship of the I/D polymorphism in ACE with ALI/ARDS in humans. Seven studies met the inclusion criteria, comprising 532 ALI/ARDS patients, 3032 healthy controls, and 1432 patients without ALI/ARDS. We used three genetic models: the allele, dominant, and recessive models. RESULTS: The ACE I/D polymorphism was not associated with susceptibility to ALI/ARDS for any genetic model. However, the ACE I/D polymorphism was associated with the mortality risk of ALI/ARDS in Asian subjects (Pallele < 0.0001, Pdominant = 0.001, P recessive = 0.002). This finding remained significant after correction for multiple comparisons. CONCLUSIONS: There is a possible association between the ACE I/D polymorphism genotype and the mortality risk of ALI/ARDS in Asians. Akihisa Matsuda and Taro Kishi These authors participated equally in this work.     

Endothelial progenitor cells: the promise of cell-based therapies for acute lung injury

Background

Endothelial progenitor cells (EPCs) are defined as a special type of stem cell that have been found to directly incorporate into injured vessels and that participate in angiogenesis and reconstruction by differentiation into endothelial cells. EPCs are widely used to therapeutically treat cardiovascular disease, limb ischemia and vascular repair. However, the role of EPCs in inflammatory diseases, especially in lung injury, is less studied.

Objective

To investigate the application of EPCs to vascular repair, and the role of EPCs in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).

Methods

A computer-based online search was performed in the PubMed database and Web of Science database for articles published, concerning EPCs, angiogenesis, ALI/ARDS and stem cell transplantation

Conclusion

EPCs have a therapeutic potential for vascular regeneration and may emerge as novel strategy for the diseases that are associated with ALI/ARDS.     

Incidence and outcome of acute lung injury and acute respiratory distress syndrome in the surgical intensive care unit

Introduction:

To determine the incidence and mortality of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in a cohort of patients with risk factors admitted to the Surgical Intensive Care Unit (SICU).

Materials and Methods:

A prospective observational inception cohort study with no intervention was conducted over 12 months. All patients with at least one known risk factor for ALI/ARDS admitted to the SICU were included in the study. The APACHE II severity of disease classification system scoring was performed within 1 h of admission. The ventilatory parameters and chest radiographs were recorded every 24 h. The P/F ratio, PEEP and Lung Injury Score were calculated each day until the day of discharge from the Intensive Care Unit or for the first 7 days of admission, whichever was shorter.

Results:

The incidence of ARDS among those who were mechanically ventilated was 11.4%. Sepsis was the most common (34.6%) etiology. Among those with risk factors, the incidence of ARDS was 30% and that of ALI was 32.7%. The mortality in those with ARDS was 41.8%. Those who develop ARDS had higher APACHE II scores, lower pH and higher PaCO₂ at admission compared with those who developed ALI or no lung injury.

Conclusion:

The incidence and mortality of ARDS was similar to other studies. Identifying those with risk factors for ARDS or mortality will enable appropriate interventional measures.     

Autocrine/paracrine mechanisms in human hematopoiesis

Autocrine/paracrine regulatory mechanisms are believed to play a role in the pathophysiology of several hematologic malignancies. Evidence is accumulating that various growth factors, cytokines, and chemokines are expressed and secreted by normal early and differentiated hematopoietic cells and thus could also regulate normal hematopoiesis in an autocrine/paracrine manner. In this review we summarize recent advances in identification and understanding of the role of autocrine/paracrine axes in the growth of both malignant and normal human hematopoietic cells. Better understanding of intercellular crosstalk operating in normal and pathological states and the mechanisms regulating synthesis of these endogenously produced factors (potential targets for various pharmacological approaches) may allow us to improve antileukemia treatments, undertake more efficient ex vivo stem cell expansion, and develop other therapeutic strategies.