急性肺损伤时肺泡上皮Na+通道研究的进展

急性肺水肿是急性肺损伤(ALI)的重要特征,肺泡上皮主动液体清除功能是影响ALI肺水肿的重要环节[1].研究表明肺泡上皮细胞钠离子通道(ENaC)是肺泡内液体主动转运的重要机制.肺泡Ⅱ型上皮细胞(ATⅡ)通过ENaC对肺泡腔的液体平衡进行调节[2-3].ALI导致肺水肿时,肺泡中的液体成分主要通过ENaC、Na+-K+-ATP酶(NKA) 和肺血管内皮细胞的水通道蛋白(AQP)重吸收.现主要对ALI时肺泡上皮ENaC的研究进展进行回顾.     

妇产科手术患者围术期发生急性肺水肿的原因分析

肺水肿是肺血管里的液体渗出至肺间质、肺泡腔和细支气管内,使肺血管外的液体量增加的一种病理状态[1]。围术期急性肺水肿常见原因:心源性、神经性液体负荷过多、毛细血管通透性增加、缺氧等[2]。肺水肿是围术期的严重并发症,抢救不及时多可致死。发     

表面活性物质在创伤性肺水肿的作用

肺表面活性物质具有降低肺泡表面张力，维持肺泡结构稳定性，防止肺萎陷和肺水肿，调节肺顺应性，阻止肺毛细血管内液体深入肺间质和肺泡内，促进肺泡内液体清除等重要功能，是维持肺正常生理功能的基础。PS系统异常与肺损伤的发生与发展密不可分，它既是肺损伤的结果，同时也是肺损伤过程中的重要内在因素。肺部伤导致的肺水肿中存在PS功能异常，创伤性肺水肿后PS含量和功能降低，其又通过多种机制加重肺水肿情况。本文着眼于创伤性肺水肿PS的变化和作用进行了综述，为临床综合治疗创伤性肺水肿提供新思路。     

血管外肺水与胸腔内血容量测定对ARDS患者诊治的指导意义

急性呼吸窘迫综合征（acute respiratory distress syndrome,ARDS）是发生于严重感染、休克、创伤及烧伤等疾病过程中,由于肺毛细血管内皮细胞和肺泡上皮细胞损伤引起弥漫性肺间质及肺泡水肿并导致的,以进行性低氧血症、呼吸窘迫为特征的临床综合征。高通透性肺水肿是ARDS的病理生理特征，肺水肿的程度与ARDS的预后呈正相关。因此，通过积极的液体管理，改善ARDS患者的肺水肿是有重要的临床意义。     

体外循环后肺功能不全的研究进展

体外循环 (cardiopulmonarybypass,CPB)可以引起重要器官功能障碍 ,急性肺损伤 (ALI)甚至急性呼吸窘迫综合征(ARDS)是其重要并发症之一。CPB后肺损伤大多数表现为亚临床症状的功能改变 ,只有少于 2 %的病人表现为ARDS[1] 。ARDS的病死率大于 5 0 % ,而且可明显延长术后恢复和住院时间。尽管对其进行了数年的研究 ,对其复杂病理生理机制的理解还很不全面。1　CPB后肺损伤的表现1 1　病理生理改变CPB后肺异常包括肺泡膜通透性和血管阻力增加 ,以及表面活性物质改变。上皮 -毛细血管内皮细胞通透性增加引起肺水肿、肺泡内蛋白聚集和…     

农村常见危重症的识别与应急处理 第五讲 急性肺水肿

急性肺水肿多由急性左心功能不全所致。左心室排血量突然不足或左心房排血受阻时,引起肺静脉及肺毛细血管压力急剧增高,当肺毛细血管内压力超过血浆胶体渗透压时,液体即从毛细血管漏出到肺间质、肺泡甚至气道内,而发生肺水肿。急性肺水肿一旦发生,病势凶险,必须及早诊断,并尽快给予紧急处理。     

无创通气治疗急性心源性肺水肿新进展

急性心源性肺水肿(ACPE)是由于心脏的原因使肺毛细血管压升高，毛细血管通透性加大引起肺血管外液体量过度增多甚至渗入肺泡，引起生理功能紊乱，如呼吸困难、缺氧等。缺氧是其突出的症状，严重缺氧可抑制心肌收缩力，诱发缺氧性脑病和肝、肾、肺等多器官衰竭而导致死亡。迅速有效地纠正缺氧，减少并发症，是抢救肺水肿的关键。     

严重脓毒症患者血管外肺水的监测价值与研究现状

脓毒症所致的多器官功能障碍中,肺脏是最易受损伤的靶器官。脓毒症相关性ARDS/ALI的发病机制复杂,迄今为止其发病机制尚未完全阐明〔1〕。其基本病理生理改变是肺泡-毛细血管屏障功能障碍所致通透性升高,表现为肺血管内液体渗出增加形成血管外肺水（extravascular lung water,EVLW）的聚集。EVLW增加引起的严重通     

有机氟中毒致中毒性肺水肿的临床救治

肺水肿是肺泡、肺毛细血管、肺间质和肺淋巴管液体交换功能失调的结果,有机氟气体具有明显亲肺毒性,吸入后经细支气管及肺泡上皮吸收,发生急性中毒性肺水肿。含氟聚合物本身无毒,不会引起急性中毒,但意外吸入生产过程中的副产品包括有     

药源性呼吸系统疾病

1药源性肺水肿 药源性肺水肿具有非心源性肺水肿的特点,一般表现为呼吸窘迫、缺氧血症及肺广泛渗出征象。在一些病情严重的患者,可能会发生肺泡毛细血管膜损害,随着富含蛋白质的液体渗入肺泡壁和肺泡内而导致肺硬化,并且损害气体交换。随着水肿液的聚积,肺顺应性和肺容量减少,导致肺内（特别是底部）小气道阻塞,致使肺下叶可听到细罗音.     

内皮祖细胞对兔急性肺损伤血管通透性的影响

目的 观察并分析内皮祖细胞对急性肺损伤兔肺血管通透性的影响。方法 将96只雄性新西兰兔分为4组：空白对照组（BC组,16只）、空白对照＋内皮祖细胞治疗组（BC＋EPC组,16只）、急性肺损伤组（ALI组,32只）、急性肺损伤＋内皮祖细胞治疗组（ALI＋EPC组,32只）。ALI组和ALI＋EPC组兔注射乳化油酸建立模型,造模成功后0．5h,ALI-EPC组和BC＋EPC组各注射约10^6个内皮祖细胞的PBS液。所有实验动物予注射乳化油酸前（哪及建立急性肺损伤模型后0．5h（T。）、6h（T2）、12h（T3）、24h（T4）、48h（T5）分别监测氧分压（PaO2）。ALI组和ALI＋EPC组兔在T2至T5,BC组和BC＋EPC组在T4至T5时间点分别处死8只兔,比较各组兔的肺湿干重比值、肺泡灌洗液（BALF）蛋白含量、肺毛细血管通透指数（LPI）、肺泡病理评分（DAD）及组织病理检查在实验前、后的变化。结果ALI＋EPC组BALF蛋白含量在T2至T5时均较ALI组显著降低,氧分压、肺湿干重比值与LPI在T3至T5时与ALI组比较差异有统计学意义,而DAD评分仅在T4和L时较ALI组显著降低（P均〈0．05）。而BC组与BC＋EPC组各指标在各时间段之间比较差异均无统计学意义（P均〉0．05）。T5时,ALI＋EPC组病理图中炎症细胞及蛋白质渗出较Au组明显好转。结论 内皮祖细胞可以改善急性肺损伤兔肺的血管通透性。     

血管内皮祖细胞介导的急性肺损伤的保护机制的研究

目的探讨体外培养的血管内皮祖细胞(EPCs)对急性肺损伤的保护作用。方法体外培养被荧光标记的EPCs,取80只BALB/C小鼠,平均分成4组,对照组(control组),急性肺损伤组(ALI组),急性肺损伤后注射EPCs组(ALI+EPCs组),无急性肺损伤注射EPCs组(EPCs组),四组分别在实验3d后同时处死后测肺水含量(EVLW)、肺通透指数(PPI),分别对其相关性进行观察和分析,并观察其肺组织冰冻切片的荧光表达。结果 ALI+EPCs组肺组织冰冻切片荧光表达EPCs量较EPCs组多,ALI组的术后肺组织EV-LW、PPI与control组和EPCs组相比有显著差异(P<0.05),ALI+EPCs组的术后EVLW、PPI与control组、ALI组和EPCs组均有显著差异(P<0.05),而control组和EPCs组的术后EVLW、PPI之间无显著差异(P>0.05)。结论体外培养的EPCs对损伤的肺血管内皮细胞有显著地趋化修复作用,因而对急性肺损伤有显著保护作用。     

Hydrostatic mechanisms may contribute to the pathogenesis of human re-expansion pulmonary edema

Objective The primary objective was to test the hypothesis that clinical re-expansion pulmonary edema is predominantly due to increased permeability of the alveolar-capillary barrier. A secondary objective was to determine if the alveolar epithelium was functionally intact in patients with re-expansion pulmonary edema by measuring net alveolar epithelial fluid transport in a subset of patients.Design Retrospective study of mechanically ventilated patients with re-expansion pulmonary edema.Setting Two academic tertiary care hospitals.Patients Seven patients with acute onset of re-expansion pulmonary edema after tube thoracostomy or thoracentesis.Interventions Pulmonary edema fluid and plasma were collected at the time of onset of re-expansion edema.Measurements and results Contrary to our hypothesis, the mean initial edema fluid to plasma protein ratio was 0.58±0.21, supporting a hydrostatic mechanism of edema formation. Four of the patients had an initial edema fluid to plasma protein ratio of less than 0.65, consistent with pure hydrostatic pulmonary edema, while the others had a slight increase in permeability (edema fluid to plasma ratios of 0.67, 0.71 and 0.77), perhaps due to capillary stress failure from hydrostatic stress. Alveolar fluid clearance (mean 9.8±8.0%/h) was intact in the subset of three patients in whom it was measured.Conclusions This study provides the first direct evidence that hydrostatic forces may contribute to the development of re-expansion pulmonary edema.This study was supported by NIH HL51856 (MAM) and NIH HL70521 (LBW)     

Bench-to-bedside review: The role of the alveolar epithelium in the resolution of pulmonary edema in acute lung injury

Clearance of pulmonary edema fluid is accomplished by active ion transport, predominantly by the alveolar epithelium. Various ion pumps and channels on the surface of the alveolar epithelial cell generate an osmotic gradient across the epithelium, which in turn drives the movement of water out of the airspaces. Here, the mechanisms of alveolar ion and fluid clearance are reviewed. In addition, many factors that regulate the rate of edema clearance, such as catecholamines, steroids, cytokines, and growth factors, are discussed. Finally, we address the changes to the alveolar epithelium and its transport processes during acute lung injury (ALI). Since relevant clinical outcomes correlate with rates of edema clearance in ALI, therapies based on our understanding of the mechanisms and regulation of fluid transport may be developed.     

Aldosterone alleviates lipopolysaccharide-induced acute lung injury by regulating epithelial sodium channel through PI3K/Akt/SGK1 signaling pathway

Reduced alveolar fluid clearance (AFC) is a major pathological feature of acute lung injury (ALI). Epithelial sodium channel (ENaC) plays a key role in regulating the transport of Na⁺ and clearing alveolar edema fluid effectively. ENaC has been reported to be regulated by aldosterone in the distal collecting tube of the kidney. We hypothesized whether aldosterone regulated ENaC in alveolar epithelium and correspondingly played a role in ALI. In this study we found that the expression of aldosterone synthesis encoding gene, CYP11B2, and ENaC were decreased in the lung tissue of LPS-induced ALI mice. Furthermore, aldosterone alleviated ALI by increasing the expression of ENaC-α and relieving pulmonary edema. Besides, we found that aldosterone upregulated ENaC-α through PI3K/Akt/SGK1 pathway. In conclusion, our study demonstrated that aldosterone attenuated pulmonary edema by upregulating ENaC-α through the PI3K/Akt/SGK1 pathway in LPS-induced ALI, indicating that aldosterone might be a promising adjuvant drug for ALI treatment.     

NLRP3 炎症体在肺损伤中的研究进展

急性肺损伤（acutelunginjury，ALI）是由多种非心源性致病因素所导致的毛细血管膜通透性增高的急性进行性低氧性呼吸功能不全或呼吸衰竭。促炎介质的释放和细胞凋亡在ALI的发生和发展过程中产生了重要的作用。尽管ALI的发病机制和治疗手段已经取得了很大的发展，但是其病死率仍然达到40％。细胞因子、炎症趋化因子和黏附分子分泌过度失调的炎症反应促进了ALI的发展。     

Alveolar epithelium and Na,K-ATPase in acute lung injury

Active transport of sodium across the alveolar epithelium, undertaken in part by the Na,K-adenosine triphosphatase (Na,K-ATPase), is critical for clearance of pulmonary edema fluid and thus the outcome of patients with acute lung injury. Acute lung injury results in disruption of the alveolar epithelial barrier and leads to impaired clearance of edema fluid and altered Na,K-ATPase function. There has been significant progress in the understanding of mechanisms regulating alveolar edema clearance and signaling pathways modulating Na,K-ATPase function during lung injury. The accompanying review by Morty et al. focuses on intact organ and animal models as well as clinical studies assessing alveolar fluid reabsorption in alveolar epithelial injury. Elucidation of the mechanisms underlying regulation of active Na⁺ transport, as well as the pathways by which the Na,K-ATPase regulates epithelial barrier function and edema clearance, are of significance to identify interventional targets to improve outcomes of patients with acute lung injury. This article refers to the articles available at: and .     

大黄对内毒素诱导致急性肺损伤的保护作用

目的：探讨内毒素在急性肺损伤（ＡＬＩ０中的作用机制及大黄,地塞米松对ＡＬＩ的保护作用。方法：在Ｗｉｓｔａｒ大鼠舌下静脉注射内毒素（ＬＰＳ）复制ＡＬＩ动物模型。动物分为４组：ＬＰＳ致伤组,对照组（生理盐水）,地塞米松治疗组,大黄治疗组。肉眼观察肺大体标本;普通光镜检查肺组织病理变化;电镜观察肺组织超微结构;测定ＡＬＩ的生物学指标;肺湿重与干重比,肺泡灌洗液中中性粒细胞比例和蛋白含量,肺泡通透指数和肺     

Science review: Mechanisms of beta-receptor stimulation-induced improvement of acute lung injury and pulmonary edema

Acute lung injury (ALI) and the acute respiratory distress syndrome are complex syndromes because both inflammatory and coagulation cascades cause lung injury. Transport of salt and water, repair and remodeling of the lung, apoptosis, and necrosis are additional important mechanisms of injury. Alveolar edema is cleared by active transport of salt and water from the alveoli into the lung interstitium by complex cellular mechanisms. Beta-2 agonists act on the cellular mechanisms of pulmonary edema clearance as well as other pathways relevant to repair in ALI. Numerous studies suggest that the beneficial effects of beta-2 agonists in ALI include at least enhanced fluid clearance from the alveolar space, anti-inflammatory actions, and bronchodilation. The purposes of the present review are to consider the effects of beta agonists on three mechanisms of improvement of lung injury: edema clearance, anti-inflammatory effects, and bronchodilation. This update reviews specifically the evidence on the effects of beta-2 agonists in human ALI and in models of ALI. The available evidence suggests that beta-2 agonists may be efficacious therapy in ALI. Further randomized controlled trials of beta agonists in pulmonary edema and in acute lung injury are necessary.     

Stimulation of alveolar epithelial fluid clearance in human lungs by exogenous epinephrine

OBJECTIVES: Because several experimental studies have demonstrated that cyclic adenosine monophosphate generation following beta-adrenoceptor activation can markedly stimulate alveolar fluid clearance, we determined whether the endogenous levels of catecholamines that occur in the pulmonary edema fluid and plasma of patients with acute lung injury are high enough to stimulate alveolar fluid clearance in the human lung. DESIGN: Observational clinical study. SETTING: Academic university hospital and laboratory. PATIENTS: Twenty-one patients with acute pulmonary edema plus ex vivo human lungs. INTERVENTIONS: Measurements of catecholamine levels in patient samples and controlled laboratory studies of the effects of these catecholamine levels on the rates of alveolar fluid clearance in ex vivo human lungs. MEASUREMENTS AND MAIN RESULTS: The concentrations of both epinephrine and norepinephrine in the pulmonary edema fluid and plasma were approximately 10 M (range of 1-8x10 M) in hydrostatic pulmonary edema (n=6) and acute lung injury patients (n=15). We therefore tested whether 10 M epinephrine or norepinephrine stimulated alveolar fluid clearance in isolated human lungs and found that these epinephrine or norepinephrine concentrations did not stimulate alveolar fluid clearance. However, higher concentrations of epinephrine (10 M), but not norepinephrine (10 M), significantly stimulated alveolar fluid clearance by 84% above control. Glibenclamide (10 M) and CFTRinh-172 (10 M), cystic fibrosis transmembrane conductance regulator inhibitors, completely inhibited the epinephrine-induced stimulation of alveolar fluid clearance. CONCLUSIONS: These results indicate that endogenous catecholamine concentrations in pulmonary edema fluid are probably not sufficient to stimulate alveolar fluid clearance. In contrast, administration of exogenous catecholamines into the distal airspaces can stimulate alveolar fluid clearance in the human lung, an effect that is mediated in part by cystic fibrosis transmembrane conductance regulator. Therefore, exogenous cyclic adenosine monophosphate-dependent stimulation will probably be required to accelerate the resolution of alveolar edema in the lungs of patients with pulmonary edema.