肺血管内皮通透功能在急性肺损伤/急性呼吸窘迫综合征发病中的损伤机制

肺血管内皮功能损伤是急性肺损伤和急性呼吸窘迫综合征重要的病理表现之一.其特征为内皮通透性增加,引起肺间质水肿,患者临床症状为呼吸窘迫、低氧血症等.肺血管内皮通透功能损伤机制尚未完全阐明,目前认为主要是作用于内皮的致伤因子和保护因子的平衡失调.本文就肺血管内皮生理功能特征、通透性损伤机制及保护机制、临床治疗措施进行综述.     

血管内皮生长因子在急性肺损伤和急性呼吸窘迫综合征作用的研究进展

简介血管内皮生长因子(VEGF)的生物学功能,探讨有关VEGF与内毒素、缺血-再灌注、高氧、通气机诱导的急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)发病机制中的作用.     

肺表面活性物质在急性肺损伤/急性呼吸窘迫综合征中的研究进展

急性肺损伤／急性呼吸窘迫综合征（ALI／ARES）时肺表面活性物质的成分、功能等均发生变化，研究这些变化对防治ALI／ARDS的发生、发展及预后，都有十分重要的意义。本文综述了肺表面活性物质在ALI／ARDS中的组成成分、代谢、功能改变以及治疗方面的研究进展，为该领域的深入研究提供参考。     

急性肺损伤/急性呼吸窘迫综合征药物治疗进展

急性肺损伤／急性呼吸窘迫综合征是全身过度炎症反应在肺部的表现,复杂的发病机制为药物治疗提供了可能的靶点,对此也进行了相当多的探索。部分药物可以改善氧合,减少机械通气时间等,但尚无一种药物被大规模多中心随机对照试验证明可以对所有患者降低死亡率,改善预后。其本身的不均一性可能有影响,对单一环节的干预效果有限。     

急性肺损伤/急性呼吸窘迫综合征药物治疗进展

急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)是临床上常见的危重症,病死率高达40%~60%,治疗措施包括机械通气及药物综合治疗。本文就糖皮质激素、外源性肺表面活性物质、血管扩张剂、蛋白酶抑制剂、及化痰药富露施、安溴索等药物在ALI/ARDS中的疗效及其可能的作用机制做一综述。     

急性肺损伤和急性呼吸窘迫综合征的药物治疗

自1967年首次报道急性呼吸窘迫综合征(ARDS)以来[1],针对ARDS的诱发因素、致病机制、诊断和治疗取得了长足的进展。在研究领域内对ARDS的认识由最早的临床征象描述进展到分子病理学和遗传易感性的分析,许多新的药物靶点不     

肺血管内巨噬细胞与急性肺损伤

肺血管内巨噬细胞（ＰＩＭ）是单核吞噬细胞系统的成员，是肺巨噬细胞亚群之一。本着重综述ＰＩＭ的结构、生物活性及其在急性肺损伤中的作用。     

急性肺损伤与急性呼吸窘迫综合征的诊治研究进展

1967年Ashbaugh首先对急性肺损伤(acutelung injury,ALI)进行描述,它是指在严重感染、休克、创伤及烧伤等非心源性疾病过程中,肺毛细血管内皮细胞和肺泡上皮细胞损伤造成弥漫性肺间质及肺泡水肿,导致的急性低氧性呼吸功能不全或衰竭。     

控制性肺膨胀在不同病因急性肺损伤中的临床观察

目的:观察控制性肺膨胀(SI)对肺部疾患、肺外疾患引起的急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)患者的疗效。方法:60例ALI/ARDS患者按病因不同分为两组,每组30例。A组:肺部疾患导致ALI/ARDS(primarily from pulmonary diseases,ARDSp)。B组:肺外疾患导致ALI/ARDS(primarily from extra-pulmo-nary diseases,ARDSexp)。均在常规治疗基础上予呼吸机辅助呼吸,实行肺保护性通气,如指氧饱和度(SpO2)低于90%,予控制性肺膨胀治疗,于治疗前后监测气道平台压(Pplat)、吸入峰压(Ppeak)、平均气道压(Pmean)、呼吸系统顺应性(Crs)、气道阻力(R)、心率(HR)、中心静脉压(CVP)、平均动脉压(MAP)及动脉血气分析。结果:B组PaO2、SpO2的改善均明显优于A组(P<0.05)。结论:肺外源性的ALI/ARDS对SI的反应优于肺内源性的ALI/ARDS。     

急性肺损伤主要生物标志物的研究进展

ALI和ARDS是由急性高渗性肺水肿引发的进行性缺氧性呼吸衰竭,有着较高的发病率和病死率。在过去十年中,大量研究在ALI患者的血浆和BALF中发现多种生物标志物,其在ALI的病理生理过程中发挥重要作用,它包括各类炎症介质、肺部各类细胞分泌的大分子以及凝血一纤溶系统相关酶类等。本文将回顾现有的主要ALI生物标志物的研究进展。     

Acetylcholine-induced pulmonary vasodilation in lung vascular injury

Recent work with isolated blood vessels has emphasized the importance of intact endothelium when the relaxation of vascular smooth muscle is induced by acetylcholine (ACh). However, the physiologic significance of this endothelial-dependent ACh response in a complete organ circulation is unclear. We questioned whether diminished ACh vasodilation would result from damage of lung vascular endothelium and whether this response could be used as an indication of endothelial injury. We therefore induced pulmonary endothelial cell injury in one rat model by repeated injections of alpha-naphthyl thiourea (ANTU) and in a second rat model by exposing rats for 52 h to 100% oxygen at a barometric pressure of 760 torr (hyperoxia). Rats injected with Tween 80, the solvent for ANTU, or exposed to ambient Denver air served as the respective control animals. The isolated lungs of these rats were perfused with a recirculating cell- and plasma-free, physiological salt solution to study the effect of ACh or NaCl infusion on pulmonary perfusion pressure and vascular responsiveness. ANTU-treated rats demonstrated an intact vasodilatory response after ACh infusion when compared with the solvent control animals. The immediate pulmonary vasodilation after ACh infusion was slightly enhanced in the hyperoxic rat lung when compared with the rats exposed to ambient air, but there was no difference between these groups in the prolonged depression of vascular responsiveness to hypoxia or angiotensin II. Thus, in both models of lung endothelial cell injury, the pulmonary vascular responses to ACh were intact.(ABSTRACT TRUNCATED AT 250 WORDS)     

糖皮质类固醇激素治疗急性肺损伤的进展

急性肺损伤(ALI)是全身炎症反应综合征在肺部的表现,炎症失控是其病变本质。糖皮质类固醇激素因其抗炎和免疫抑制特性而被广泛应用于临床重症疾病。本文在复习近年来文献的基础上就糖皮质激素在ALI中的应用进展作一综述。     

The coagulation system and pulmonary endothelial function in acute lung injury

Acute lung injury (ALI) is a disease marked by diffuse endothelial injury and increased capillary permeability. The coagulation system is a major participant in ALI and activation of coagulation is both a consequence and contributor to ongoing lung injury. Increased coagulation and depressed fibrinolysis result in diffuse alveolar fibrin deposition which serves to amplify pulmonary inflammation. In addition, existing evidence demonstrates a direct role for different components of coagulation on vascular endothelial barrier function. In particular, the pro-coagulant protein thrombin disrupts the endothelial actin cytoskeleton resulting in increased endothelial leak. In contrast, the anti-coagulant activated protein C (APC) confers a barrier-protective actin configuration and enhances the vascular barrier in vitro and in vivo. However, recent studies suggest a complex landscape with receptor cross-talk, temporal heterogeneity and pro-coagulant/anti-coagulant protein interactions. In this article, the major signaling pathways governing endothelial permeability in lung injury are reviewed with a particular focus on the role that endothelial proteins, such as thrombin and APC, which play on the vascular barrier function.     

Prospects for gene therapy in acute lung injury.

Gene transfection is an extremely useful tool with which to explore mechanisms of gene regulation, to examine the molecular physiology of proteins in cultured cells, and to produce transgenic organisms. Several transfection techniques that employ viral and nonviral vectors have been used successfully to transfect functional genes into lung cells in vivo. This report reviews some of the gene transfection techniques that have been applied to the intact lung, an organ that offers unique challenges and opportunities. Results indicate that somatic cell gene therapy is feasible and that gene-based therapies can be developed for acute and chronic lung diseases.     

Cell-based angiopoietin-1 gene therapy for acute lung injury

RATIONALE: The acute respiratory distress syndrome is a significant cause of morbidity and mortality in critically ill patients. Angiopoietin-1 (Ang-1), a ligand for the endothelial Tie2 receptor, is an endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-endothelium interactions. OBJECTIVES: We hypothesized that Ang-1 counteracts vascular inflammation and pulmonary vascular leak in experimental acute lung injury. METHODS: We used cell-based gene therapy in a rat model of ALI. Transgenic mice overexpressing Ang-1 or deficient in the Tie2 receptor were also studied to better elucidate the mechanisms of protection. MEASUREMENTS AND MAIN RESULTS: The present report provides data that support a strong protective role for the Ang-1/Tie2 system in two experimental models of LPS-induced acute lung injury. In a rat model, cell-based Ang-1 gene transfer improved morphological, biochemical, and molecular indices of lung injury and inflammation. These findings were confirmed in a gain-of-function conditional, targeted transgenic mouse model, in which Ang-1 reduced endothelial cell activation and the expression of adhesion molecules, associated with a marked improvement in airspace inflammation and intraalveolar septal thickening. Moreover, heterozygous Tie2-deficient mice demonstrated enhanced evidence of lung injury and increased early mortality. CONCLUSIONS: These results support a critical role for the Ang-1/Tie2 axis in modulating the pulmonary vascular response to lung injury and suggest that Ang-1 therapy may represent a potential new strategy for the treatment and/or prevention of acute respiratory distress syndrome in critically ill patients.     

Fas-induced pulmonary apoptosis and inflammation during indirect acute lung injury

RATIONALE: Indirect acute lung injury (ALI) is associated with high morbidity and mortality. No specific therapies have been developed, because the underlying pathophysiological processes remain elusive. OBJECTIVES: To investigate the contribution of Fas-induced apoptotic and nonapoptotic/inflammatory signaling to the pathology of indirect ALI. METHODS: A mouse model of indirect ALI, induced by successive exposure to hemorrhagic shock and cecal ligation and puncture, was used. Quantification of active caspase-3 and the short splice variant of FLICE-inhibitory protein, (FLIP)short, was performed by Western blotting and immunohistochemistry, and cytokines/chemokines were assessed by cytometric bead array or ELISA. M30 immunostaining was done to evaluate epithelial cell apoptosis. Lung injury was assessed on the basis of myeloperoxidase activity, bronchoalveolar lavage protein, and lung histology. MEASUREMENTS AND MAIN RESULTS: Twelve hours after insult, lung monocyte chemoattractant protein-1, keratinocyte-derived chemokine, macrophage inflammatory protein-2, IL-6, tumor necrosis factor-alpha, and caspase-3 were increased and FLIP(short) was decreased. Fas- and Fas ligand-deficient mice showed marked protection from lung inflammation and apoptosis and decreased ALI. This was associated with a 10-day survival benefit. Similarly, 4 hours after pulmonary instillation of Fas-activating antibody in vivo, lung chemokines were markedly elevated in background mice and, interestingly, to a similar degree in macrophage-deficient animals. Fas activation on lung epithelial cells in vitro led to chemokine production that was dependent on extracellular signal-regulated kinase. CONCLUSIONS: Activation of apoptotic and nonapoptotic/inflammatory Fas signaling is an early important pathophysiological event in the development of indirect ALI after hemorrhagic shock and sepsis, in which lung epithelial cells appear to play a central role.