肺泡巨噬细胞在急性肺损伤中的作用

肺泡巨噬细胞作为常驻肺部的主要固有免疫细胞,在急性肺损伤(ALI)的发生、发展以及转归过程中发挥了十分重要的作用.在ALI早期,肺部固有巨噬细胞通过释放趋化因子募集更多的外周巨噬细胞及中性粒细胞至炎症部位,启动肺部炎症反应.随着炎症的进一步发展,肺泡巨噬细胞功能的适度发挥调节中性粒细胞的过度激活从而控制炎症的失控性进展.在ALI晚期,肺泡巨噬细胞再次通过清除凋亡的炎症细胞加速炎症的消退,从而影响ALI的转归及预后.     

急性肺损伤发病机制的研究进展

急性肺损伤（ALI）是临床常见的急危重症,病死率高,多年来对其发病机制进行了大量的研究。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,本文将对近年来的研究做一综述。     

炎症介质与内毒素肺损伤

急性肺损伤 (ALI)是临床上一种常见的危重病症 ,内毒素是导致ALI的重要因素。各种炎症介质在内毒素肺损伤的发病中起重要作用。本文对参与内毒素肺损伤发病的细胞因子及其它炎症介质作一简要综述     

机械通气与急性肺损伤和多器官功能失常综合征的关系

急性肺损伤和急性呼吸窘迫综合征（ALI／ARDS）患者在治疗过程中常因并发多器官功能失常综合征和多器官功能衰竭（MODS／MOF）而使病情加重,甚至死亡。迄今从ALI／ARDS发展到MODS／MOF的机制尚未完全阐明。机械通气（MV）是治疗ALI／ARDS的主要方法之一。有研究表明呼吸机使用不当不仅可加重ALI／ARDS已有的肺损伤和炎症反应,还可能促进肺内炎性细胞和炎症介质进入血液,从而诱发或加重MODS／MOF。本文就MV与ALI／ARDS、肺部炎症和MODS／MOF的关系进行阐述。     

炎症介质与内毒素肺损伤

急性肺损伤(ALI)是临床上一种常见的危重病症．内毒素是导致ALI的重要因素。各种炎症介质在内毒素肺损伤的发病中起重要作用。本文对参与内毒素肺损伤发病的细胞因子及其它炎症介质作一简要综述。     

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。     

丹参水提物对急性肺损伤保护作用的实验研究

急性肺损伤 (ALI)是由多种炎症细胞参与的肺脏局部炎症反应和炎症反应失控所致的肺毛细血管膜损伤。近年发现胞间黏附分子 1(ICAM 1)的黏附功能是参与炎症性疾病的重要病理生理基础[1] 。ALI发病机制十分复杂 ,至今仍未完全阐明 ,临床亦无特异有效的防治措施。我们静脉注射油酸复制大鼠ALI模型 ,通过观察肺组织ICAM 1表达及肺组织损伤性改变 ,探讨丹参水提物对ALI的保护作用。材料与方法　Wistar大鼠 5 4只 ,雌雄各半 ,体重 2 0 0～2 4 0g ,平均体重 (2 2 6± 12 )g ,由贵州省实验动物中心提供。按随机数字表法分成正常对照组、模…     

急性肺损伤/急性呼吸窘迫综合征的诊断标准(草案)

一、定义急性肺损伤／急性呼吸窘迫综合征（ALI／ARDS）是指由心源性以外的各种肺内外致病因素导致的急性、进行性缺氧性呼吸衰竭。ALI和ARDS具有性质相同的病理生理改变,严重的ALI被定义为ARDS。ALI／ARDS的病理基础是由多种炎症细胞（巨噬细胞、嗜中性粒细胞和淋巴细胞等）介导的肺脏局部炎症反应和炎症反应失控所致的肺毛细血管膜损伤。其主要病理特征为由肺微血管通透性增高而导致的肺泡渗出液中富含蛋白质的肺水肿及透明膜形成,可伴有肺间质纤维化。病理生理改变以肺顺应性降低,肺内分流增加及通气血流比例失衡为主。临…     

参麦注射液对脂多糖诱导大鼠急性肺损伤防护机制探讨

在急性肺损伤（ALI）发病过程中，促炎细胞因子和抑炎细胞因子的共同作用介导着炎症的发生和发展。本组研究应用静脉注射脂多糖（LPS）复制大鼠ALI模型，观察参麦注射液对LPS所致大鼠ALI的作用。     

效应细胞与内毒素肺损伤

急性肺损伤 (ALI)是临床上一种常见的危重病症 ,内毒素是导致ALI的重要因素。效应细胞及其激活后释放的细胞因子等炎症介质在内毒素肺损伤的发病中起重要作用。本文对参与内毒素肺损伤发病的效应细胞作一简要综述     

NLRP3炎症小体在海水吸入性急性肺损伤中的表达和作用

目的探讨海水吸入型急性肺损伤大鼠肺组织中NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体表达的变化及介导的炎性因子在急性肺损伤(ALI)发生发展中的作用。 方法将50只健康雄性SD大鼠随机分为5组,对照组,海水吸入1 h组,海水吸入3 h组,海水吸入6 h组,海水吸入9 h组,每组10只。采用经气管缓慢滴注(3 ml/kg)海水的方法制作大鼠损伤模型。制作大鼠肺脏石蜡切片并HE染色观察病理形态学变化。检测大鼠肺组织湿干比。ELISA检测测定各组肺组织中IL-1β和IL-18水平,RT-PCR检测肺组织中IL-1β、IL-18和NLRP3mRNA的表达。Western-blot检测肺组织中NLRP3蛋白表达。 结果气管滴注海水后成功复制海水吸入性急性肺损伤模型。肺组织湿干比较对照组显著升高。病理形态学观察可见肺组织大量炎细胞浸润、水肿、间质增厚。各组大鼠血清中IL-1β和IL-18的水平随着时间增加逐渐升高,且在3～6 h达到顶峰,随后炎症因子的表达逐渐降低。与空白对照组比较,差异均有统计学意义(均P<0.05)。各组大鼠肺组织中IL-1β和IL-18的mRNA的表达水平与大鼠肺组织中IL-1β和IL-18的表达基本一致。与空白对照组比较,差异均有统计学意义(均P<0.05)。肺组织匀浆中NLRP3转录和翻译结果显示海水吸入刺激后,肺组织中NLRP3的mRNA和NLRP3蛋白含量变化含量随着时间明显逐渐增加,差异均有统计学意义(均P<0.05)。 结论海水刺激下,NLRP3炎症小体介导的炎症反应参与了急性肺损伤发病过程并加重了肺损伤的程度,可能是海水急性肺损伤的发病机制之一,但其作用有待进一步证实。     

The role of inflammation in respiratory impairment during Pneumocystis carinii pneumonia

Pneumocystis carinii remains an important cause of pneumonia in immunosuppressed hosts. Severe Pneumocystis pneumonia is characterized by an intense neutrophilic inflammatory response resulting in gas exchange abnormalities, diffuse alveolar damage, and respiratory failure. The inflammatory response directed against P. carinii involves a complex series of interactions between alveolar macrophages, CD4+ T lymphocytes, polymorphonuclear cells, and their various products. CD4+ T lymphocytes are crucial to host defense against P. carinii. Alveolar macrophages also provide essential functions that significantly enhance clearance of P. carinii infection. In addition, host proteins play an important role in augmenting the host inflammatory responses to this organism. Although essential for effective clearance of infection, excessive inflammatory responses also predispose the host to the development of lung injury and respiratory compromise. Understanding the complex processes involved in the host inflammatory response and its potential for causing lung injury may enable development of novel therapeutic approaches for this and other important fungal lung infections.     

呼吸机相关性肺损伤与炎症反应

呼吸机相关性肺损伤是由于机械牵张和高浓度氧吸入等因素触发多种肺组织细胞的感受器,激活阳离子通道、模式识别受体、丝裂原活化蛋白激酶等多种信号传导通路,引起细胞因子、趋化因子和黏附分子的合成与释放,诱发过度炎症反应,造成肺组织损伤。因此,对呼吸机相关性肺损伤中炎症反应的触发机制、作用通路及炎症因子做深入研究,可以为呼吸机相关性肺损伤的防治工作提供借鉴。     

p38MAPK抑制剂与急性肺损伤的保护

急性肺损伤可由多种诱因引起,是急性呼吸衰竭最主要部分,死亡率高.p38MAPK信号转导途径参与急性肺损伤的发生、发展.p38MAPK抑制剂是一类合成的小分子有机化合物,通过特异性阻断p38减少急性肺损伤时炎症因子表达,改善血流动力学,减轻组织损伤,有望成为急性肺损伤治疗的新途径.     

Doxycycline attenuated lung injury by its biological effect apart from its antimicrobial function

Antibiotics can have a biological effect apart from their anti-bacterial effect. We hypothesized that doxycycline could attenuate acute lung injury through its biological effect. Lipopolysaccharide or doxycycline-resistant Streptococcus pneumoniae was administered intratracheally into mice with the co-administration of doxycycline. Thereafter, the lung pathology, intraalveolar inflammatory cells, bacterial number, and matrix metalloproteinases were investigated. Matrix metalloproteinases, neutrophil migration, and alveolar destruction were induced by lipopolysaccharide. Doxycycline was thus found to improve all of these symptoms. In addition, an inhibitor of matrix metalloproteinases, CGS27023A, attenuated lipopolysaccharide-induced lung injury. Doxycycline also attenuated the lung injury induced by doxycycline-resistant S. pneumoniae and improved the mortality rate although the bacterial number in the lung did not change. Our data indicated that doxycycline could attenuate acute lung injury through a biological effect that was different from its antibiotic effect.     

Sepsis syndrome, the adult respiratory distress syndrome, and nosocomial pneumonia. A common clinical sequence

Systemic sepsis and pneumonia are common predisposing factors for ARDS, which can serve as the initial manifestation of the multisystem organ failure syndrome. Primary pneumonia that necessitates ICU admission leads to ARDS in approximately 10% of patients. Systemic infection can also lead to ARDS, but when bacteremia alone is present, the risk is low (probably less than 5%). If the septic syndrome with a hemodynamic and end-organ response develops, the ARDS may follow in as many as 40% of patients. When multiple risk factors for acute lung injury are present, the risk of developing ARDS rises dramatically. The septic syndrome, acute lung injury, and multiorgan failure are closely tied to one another because bacterial cell walls can activate inflammatory mediators, such as interleukin-1 and tumor necrosis factor, which can in turn lead to the septic syndrome and inflammatory injury to the lung. Clinical features, more than serum markers, have been the best predictors of whether lung injury will follow sepsis, indicating that the mere presence of mediators alone cannot cause ARDS and that there are individual susceptibility factors in the effects of these mediators. With the advent of monoclonal antibodies and new anti-inflammatory drugs, prevention of progression from sepsis to multiorgan failure may become possible. Pneumonia is the most common infection that complicates ARDS once it is established, and the mortality rate may approach 90%. The existence of acute lung injury, its predisposing conditions, coexisting illnesses, and the therapeutic interventions used for patients with lung injury all can interfere with lung host defenses and set the stage for bacterial infection of the already-injured lung. This infection appears to add to the propagation of the multiple system organ failure that has already begun. In the future, it may become possible to prevent this infection, which would be a welcome development, because currently, we are stymied in our efforts to diagnose and treat pneumonia in the setting of acute lung injury. Preventive efforts will follow from an understanding of the pathogenesis of pneumonia and in the future may include topical antibiotics, selective digestive decontamination, and prophylactic passive immunotherapy.     

Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury

RATIONALE: Acute inflammation and vascular leak are cardinal features of acute lung injury and the acute respiratory distress syndrome. Nonspecific tissue inflammation and injury in response to infectious and noninfectious insults lead to oxidative stress and the generation of lipid oxidation products, which may inhibit the acute inflammatory response to bacterial components. OBJECTIVE: To test the hypothesis that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) may attenuate the acute lung inflammatory response to lipopolysaccharide (LPS) and enhance lung vascular barrier recovery, we used in vivo and in vitro models of LPS-induced lung injury. METHODS: Rats received intratracheal aerosolized LPS (5 mg/kg) or sterile water with concurrent intravenous injection of OxPAPC (0.5-6.0 mg/kg) or saline alone. Nonoxidized PAPC was used as a control. At 18 h, bronchoalveolar lavage was performed and the lungs were removed for histologic analysis. Measurements of endothelial transmonolayer electrical resistance and immunofluorescent analysis of monolayer integrity were used in an in vitro model of LPS-induced lung vascular barrier dysfunction. MEASUREMENTS AND MAIN RESULTS: In vivo, aerosolized intratracheal LPS induced lung injury with profound increases in bronchoalveolar lavage neutrophils, protein content, and the inflammatory cytokines interleukin 6 and interleukin 1beta, as well as tissue neutrophils. OxPAPC, but not nonoxidized PAPC, markedly attenuated the LPS-induced tissue inflammation, barrier disruption, and cytokine production over a range of doses. In vitro, oxidized phospholipids attenuated LPS-induced endothelial barrier disruption and reversed LPS-induced cytoskeletal remodeling and disruption of monolayer integrity. CONCLUSIONS: These studies demonstrate in vivo and in vitro protective effects of oxidized phospholipids on LPS-induced lung dysfunction.     

Mizoribine protects against bleomycin-induced lung injury

Bleomycin (BLM)-induced lung injury has become a model for studies of interstitial pneumonitis and pulmonary fibrosis. BLM induces lung injury in two phases: early inflammation characterized by infiltration of inflammatory cells into the lungs, followed by a late phase of fibrosis characterized by deposition of collagen. In this study, we examined the role of mizoribine (MZB) in the regulation of inflammatory tissue injury caused by BLM. We examined the role of MZB using a mouse model of BLM-induced lung injury. We demonstrated that mice subjected to instillation of BLM into the lungs had a significantly increased number of macrophages and lymphocytes in bronchoalveolar lavage fluid (BALF), but that those treated with MZB in the early phase showed a significant reduction in the total number of BALF macrophages and lymphocytes. However, MZB was unable to inhibit fibrosis in the late phase of BLM injury. Our findings suggest that MZB inhibits the proliferation of both lymphocytes and macrophages in the early phase of the BLM-induced acute inflammatory response, as well as its development and amplification, but does not inhibit fibrotic change in the late phase.     

中性粒细胞活化和上皮细胞凋亡在急性肺损伤发生中的作用

致病因子一方面诱导肺泡巨噬细胞和上皮细胞产生多种细胞因子和趋化因子,激活中性粒细胞并使其向损伤部位聚集,从而产生炎症因子的瀑布式反应;另一方面激活死亡受体通路Fas-FasL等诱发肺上二皮细胞凋亡,从而引起肺组织损伤.另外,Fas活化后可通过介导肺内炎症介质释放和中性粒细胞聚集进一步加重肺损伤.中性粒细胞活化和上皮细胞凋亡在急性肺损伤的发生过程中起重要作用.