miR-146b overexpression ameliorates lipopolysaccharide-induced acute lung injury in vivo and in vitro

Acute respiratory distress syndrome (ARDS) is a type of acute lung injury (ALI), which causes high morbidity and mortality. So far, effective clinical treatment of ARDS is still limited. Recently, miR-146b has been reported to play a key role in inflammation. In the present study, we evaluated the functional role of miR-146b in ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. The miR-146b expression could be induced by LPS stimulation, and miR-146b overexpression was required in the maintenance of body weight and survival of ALI mice; after miR-146b overexpression, LPS-induced lung injury, pulmonary inflammation, total cell and neutrophil counts, proinflammatory cytokines, and chemokines in bronchial alveolar lavage (BAL) fluid were significantly reduced. The promotive effect of LPS on lung permeability through increasing total protein, albumin and IgM in BAL fluid could be partially reversed by miR-146b overexpression. Moreover, in murine alveolar macrophages, miR-146b overexpression reduced LPS-induced TNF-α and interleukin (IL)-1β releasing. Taken together, we demonstrated that miR-146b overexpression could effectively improve the LPS-induced ALI; miR-146b is a promising target in ARDS treatment.     

急性肺损伤的生物标记物

急性呼吸窘迫综合征(ARDS)和急性肺损伤(ALI)多由低氧性呼吸衰竭引起,导致高通透性肺水肿,临床上有较高的发病率与死亡率。近十年来,针对血浆和支气管肺泡灌洗液中相关生物标记物的研究为探索急性肺损伤的病理生理机制指明了新的方向。个别生物标记物已在一些大型、多中心ARDS试验中得到证实。但迄今仍没有一个或一组生物标记物常规应用于临床。随着人类对ALI发病机制理解的进一步深入,或许不久的将来,生物标记物会真正应用于评估疾病的严重程度和预后。本文将概述近年来ALI相关生物标记物的研究进展。     

乌司他丁对急性肺损伤/急性呼吸窘迫综合征的治疗研究

目的研究大剂量乌司他丁在急性肺损伤/急性呼吸窘迫综合征中的治疗效果。方法回顾性分析2006年1月至2010年1月广西医科大学第一附属医院ICU收治的154例ALI/ARDS患者的临床资料,根据治疗方案分为乌司他丁组(UTI组)(n=80),对照组(n=74)。记录两组患者开始治疗、治疗第3天、治疗第7天的生命体征、动脉血气分析、血生化检查结果;记录患者在ICU治疗的转归。应用SPSS 13.0软件对结果进行统计学分析。结果经治疗3天UTI组呼吸频率低于对照组;动脉血气分析提示两组患者PaO2、PaO2/Fi O2、SaO2均有上升,UTI组PaO2/Fi O2略低于对照组(P0.01),而两组患者PaO2、SaO2比较无统计学差异。UTI组与对照组的死亡率比较(UTI组52.5%,对照组52.7%,P=0.980)无统计学差异,机械通气时间UTI组低于对照组[UTI组(14.8±3.9)天,对照组(16.7±4.2)天,P=0.020]。根据ALI/ARDS发生的病因分为肺内源性及肺外源性进行亚组分析(A组:肺内源性ALI/ARDS,使用UTI治疗;B组:肺内源性ALI/ARDS,不使用UTI治疗;C组:肺外源性ALI/ARDS,使用UTI治疗;D组:肺外源性ALI/ARDS,不使用UTI治疗),发现乌司他丁对肺外源性ALI/ARDS患者(C组)的ICU时间、ICU内死亡率及机械通气时间均低于不使用UTI的患者(D组)。结论大剂量乌司他丁用于ALI/ARDS的临床治疗可有效改善患者氧合指数,减少机械通气时间,且高血糖的发生率低,尤其是乌司他丁治疗肺外源性ALI/ARDS患者的预后优于肺内源性的ALI/ARDS。     

Contribution of neutrophil-derived myeloperoxidase in the early phase of fulminant acute respiratory distress syndrome induced by influenza virus infection

Because the pathogenesis of acute respiratory distress syndrome (ARDS) induced by influenza virus infection remains unknown, we can only improve on existing therapeutic interventions. To approach the subject, we investigated immunological etiology focused on cytokines and an acute lung damage factor in influenza-induced ARDS by using a PR-8 (A/H1N1)-infected mouse model. The infected mouse showed fulminant severe pneumonia with leukocyte infiltration, claudin alteration on tight junctions, and formation of hyaline membranes. In addition to interferon (IFN)-α, plenty of keratinocyte-derived chemokines (KC), macrophage inflammatory protein 2 (MIP-2), regulated on activation normal T-cell expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1) were significantly released into bronchoalveolar lavage fluid (BALF) of the model. We focused on neutrophil myeloperoxidase (MPO) as a potent tissue damage factor and examined its contribution in influenza pneumonia by using mice genetically lacking in MPO. The absence of MPO reduced inflammatory damage with suppression of leakage of total BALF proteins associated with alteration of claudins in the lung. MPO(-/-) mice also suppressed viral load in the lung. The present study suggests that MPO-mediated OCl(-) generation affects claudin molecules and leads to protein leakage and viral spread as a damage factor in influenza-induced ARDS.     

油酸致兔ARDS模型长期效果的多因素析评

目的:研究油酸致ARDS模型对疾病的长期模拟效果,并探讨内在机制。方法:选择健康新西兰大白兔30只,经左侧耳缘静脉按油酸0.1 ml/kg的剂量缓慢注入,观察动物呼吸、心率变化,测定氧合指数(PaO2/FiO2)、动脉氧分压、二氧化碳分压。分别于注射油酸后6小时、24小时、48小时以及72小时处死动物,收集静脉血及肺泡灌洗液(BALF),ELISA法检测肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)变化。H-E染色镜下观察肺部病理改变,计算肺组织含水量以判断肺损伤程度。结果:①所有模型动物在6小时内均出现ARDS表现。②6h组、24h组以及48h组氧合指数(PaO2/FiO2)与正常对照组相比均明显降低(P<0.05),且符合ARDS诊断标准。72h组氧合指数(PaO2/FiO2)虽然也明显降低,但未达到ARDS的诊断标准。③血浆中TNF-α与IL-6明显升高(P<0.05),于致伤后72小时后有所恢复,但仍高于正常。BALF中TNF-α也出现相同变化趋势,而IL-6则在试验期间持续高表达。④镜下可见两肺充血、出血,肺泡及肺间质水肿,透明膜形成,大量中性粒细胞浸润,终末支气管上皮细胞变性坏死,双肺含水...     

机械通气治疗急性呼吸窘迫综合征的肺复张策略研究

目的:探讨机械通气治疗急性呼吸窘迫综合征(Acute respiratory distress syndrome,ARDS)的肺复张策略的作用。方法:选择2012年1月~2012年12月我院收治的采用机械通气并进行肺复张治疗的ARDS患者94例,根据肺复张方法不同,将所有患者分为对照组和实验组,并比较两组患者的不同时点的氧合指数、肺顺应性及两组出现的并发症。结果:对照组肺复张成功率为72.34%,实验组肺复张成功率为95.75%,X2=38.928,P0.05,两组患者肺复张成功率差异具有统计学意义。两组患者氧合指数、肺顺应性和PaCO2在肺复张实施前比较,差异无统计学意义。肺复张策略实施后24h、48h和72h的氧合指数和PaCO2比较,这三个时点的氧合指数和PaCO2差异具有统计学意义。两组患者肺顺应性在肺复张策略实施后1h、2h和6h比较,t分别=4.939,5.391和5.999,P0.05,此三个时点的肺顺应性差异同样具有统计学意义。对照组气压伤发生率为82.98%,实验组气压伤发生率为59.57%,两组患者气压伤发生率差异具有统计学意义。结论:ARDS的患者在机械通气治疗的过程中上采用肺复张策略,不但可以提高肺复张成功率,改善肺部通气效果,且安全性好,适合临床使用。     

Current status and prospects of basic research and clinical application of mesenchymal stem cells in acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a common and clinically devastating disease that causes respiratory failure. Morbidity and mortality of patients in intensive care units are stubbornly high, and various complications severely affect the quality of life of survivors. The pathophysiology of ARDS includes increased alveolar–capillary membrane permeability, an influx of protein-rich pulmonary edema fluid, and surfactant dysfunction leading to severe hypoxemia. At present, the main treatment for ARDS is mechanical treatment combined with diuretics to reduce pulmonary edema, which primarily improves symptoms, but the prognosis of patients with ARDS is still very poor. Mesenchymal stem cells (MSCs) are stromal cells that possess the capacity to self-renew and also exhibit multilineage differentiation. MSCs can be isolated from a variety of tissues, such as the umbilical cord, endometrial polyps, menstrual blood, bone marrow, and adipose tissues. Studies have confirmed the critical healing and immunomodulatory properties of MSCs in the treatment of a variety of diseases. Recently, the potential of stem cells in treating ARDS has been explored via basic research and clinical trials. The efficacy of MSCs has been shown in a variety of in vivo models of ARDS, reducing bacterial pneumonia and ischemia-reperfusion injury while promoting the repair of ventilator-induced lung injury. This article reviews the current basic research findings and clinical applications of MSCs in the treatment of ARDS in order to emphasize the clinical prospects of MSCs.     

Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice

Background

Human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) attenuate hyperoxic neonatal lung injury primarily through anti-inflammatory effects. We hypothesized that intratracheal transplantation of human UCB-derived MSCs could attenuate Escherichia coli (E. coli)-induced acute lung injury (ALI) in mice by suppressing the inflammatory response.

Methods

Eight-week-old male ICR mice were randomized to control or ALI groups. ALI was induced by intratracheal E. coli instillation. Three-hours after E. coli instillation, MSCs, fibroblasts or phosphate-buffered saline were intratracheally administered randomly and survival was analyzed for 7 days post-injury. Lung histology including injury scores, myeloperoxidase (MPO) activity, and protein levels of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein (MIP)-2 as well as the wet-dry lung ratio and bacterial counts from blood and bronchoalveolar lavage (BAL) were evaluated at 1, 3, and 7 days post-injury. Levels of inflammatory cytokines in the lung were also profiled using protein macroarrays at day 3 post-injury which showed peak inflammation.

Results

MSC transplantation increased survival and attenuated lung injuries in ALI mice, as evidenced by decreased injury scores on day 3 post-injury and reduced lung inflammation including increased MPO activity and protein levels of IL-1α, IL-1β, IL-6, TNF-α, and MIP-2 on day 3 and 7 post-injury. Inflammatory cytokine profiles in the lungs at day 3 post-injury were attenuated by MSC transplantation. MSCs also reduced the elevated lung water content at day 3 post-injury and bacterial counts in blood and BAL on day 7 post-injury.

Conclusions

Intratracheal transplantation of UCB-derived MSCs attenuates E. coli-induced ALI primarily by down-modulating the inflammatory process and enhancing bacterial clearance.     

Acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) can be associated with various disorders. Among these, coronavirus infection may cause life-threatening severe acute respiratory syndrome (SARS). In this review, we present animal models and techniques for the study of ARDS, and discuss the roles and possible mechanisms of various chemical factors, including nitric oxide (NO). Our early work revealed that cerebral compression elicits severe hemorrhagic pulmonary edema (PE), leading to central sympathetic activation that results in systemic vasoconstriction. The consequence of systemic vasoconstriction is volume and pressure loading in the pulmonary circulation. Vasodilators, but not oxidant radical scavengers, are effective in the prevention of centrogenic PE. In isolated perfused lung, exogenous and endogenous NO enhances lung injury following air embolism and ischemia/reperfusion. In contrast, NO synthase (NOS) inhibitors reverse such lung injury. Although NO is important in maintaining vasodilator tone, hypoxia-induced pulmonary vasoconstriction is accompanied by an increase instead of a decrease in NO release. In animal and isolated lung studies, endotoxin produces acute lung injury that is associated with increases in cytokines and inducible NOS mRNA expression, suggesting that NO is toxic to the lung in endotoxin shock. Recently, we reported several rare cases that indicate that ARDS in patients with Japanese B encephalitis, lymphangitis with breast cancer and fat embolism is caused by different mechanisms. Our early and recent studies on ARDS and PE may provide information for clinical practice and the understanding of the pathogenesis of SARS.     

细胞因子在ARDS发病机制中的作用

细胞因子是由多种细胞产生的多肽或低分子糖蛋白,在人体内含量极微,在pg水平就发挥作用。作为特异性免疫反应和非特异性免疫反应的蛋白质,细胞因子以自分泌、旁分泌、或内分泌方式产生,与相应的细胞表面受体结合,在局部或全身发挥复杂的生物学效应,它们的代谢异常和疾病的发生、发展有着密切的关系。有些细胞因子已应用于临床的生物学治疗,具有深远的临床应用价值,故对细胞因子的研究将是一个越来越重要的课题。急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)发病机制错综复杂,大量临床和实验室研究证明多种效应细胞释放的炎症介质是造成ARDS的"中心环节",其中TNF-α、IL-1、IL-8、IL-10、CXC趋化因子等细胞因子在ARDS发病中的作用尤为重要。本文就细胞因子在ARDS发病机制中的作用做一综述。     

Urinary desmosine as a biomarker in acute lung injury

Acute lung injury (ALI) is a complex disorder associated with an acute inflammatory response thought to contribute to tissue injury. Desmosine, a cross-linking amino acid present in elastin, is released during matrix degradation and cleared by the kidney. Results from animal models and human disease studies have suggested that ALI is associated with the release of desmosine, resulting in increased urinary desmosine. A radioimmunoassay was used to monitor urinary desmosine levels over 10 days in ten patients with ALI. The concentration of desmosine was measured with and without acid hydrolysis. Baseline urinary desmosine was increased in two of ten patients. The concentration of desmosine at baseline did not appear to be related to age, gender, neutrophil elastase (NE)/α₁-antiprotease complex concentration or P_aO₂/F_iO₂ ratio. No meaningful changes in desmosine levels were noted after removal from mechanical ventilation. Baseline desmosine concentrations did not appear to correlate with the risk of death. The limited sensitivity, predictive correlations and dynamic modulation would suggest that urine desmosine has a limited role as a biomarker for ALI. Hydrolysis of urine samples appears necessary for optimal measurement of urine desmosine.     

Bronchoalveolar fluid and plasma inflammatory biomarkers in contemporary ARDS patients

Purpose: Bronchoalveolar fluid (BALF) and plasma biomarkers are often endpoints in early phase randomized trials (RCTs) in acute respiratory distress syndrome (ARDS). With ARDS mortality decreasing, we analyzed baseline biomarkers in samples from contemporary ARDS patients participating in a prior RCT and compared these to historical controls.

Materials and methods: Ninety ARDS adult patients enrolled in the parent trial. BALF and blood were collected at baseline, day 4?±?1, and day 8?±?1. Interleukins-8/-6/-1β/-1 receptor antagonist/-10; granulocyte colony stimulating factor; monocyte chemotactic protein-1; tumour necrosis factor-α; surfactant protein-D; von Willebrand factor; leukotriene B₄; receptor for advanced glycosylation end products; soluble Fas ligand; and neutrophil counts were measured.

Results: Compared to historical measurements, our values were generally substantially lower, despite our participants being similar to historical controls. For example, our BALF IL-8 and plasma IL-6 were notably lower than in a 1999 RCT of low tidal volume ventilation and a 2007 biomarker study, respectively.

Conclusions: Baseline biomarker levels in current ARDS patients are substantially lower than 6–20?years before collection of these samples. These findings, whether from ICU care changes resulting in less inflammation or from variation in assay techniques over time, have important implications for design of future RCTs with biomarkers as endpoints.     

大承气汤辅助治疗ARDS患者对其pH、PaO2/FiO2和氧化应激状态的影响

目的:观察大承气汤辅助治疗ARDS患者对其pH、氧合指数(PaO_2/FiO_2)及氧化应激状态的影响。方法:选择2014年8月~2016年8月于成都中医药大学临床医学院就诊的82例ARDS患者,按治疗方式的不同随机分为对照组与实验组,对照组接受常规治疗,实验组在对照组的基础上联合大承气汤治疗,两组均持续用药7天。观察两组ICU住院时间、机械通气时间、不良反应的发生情况、治疗前后pH、PaO_2/FiO_2、血气超氧化物歧化醇(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醇(MDA)水平的变化。结果:实验组ICU住院时间、机械通气时间及不良反应的发生率均显著短于或低于对照组(P0.05)。治疗前,两组pH、PaO_2/FiO_2、血清SOD、GSH-Px、MDA水平比较差异无统计学意义(P0.05);治疗后,两组pH、PaO_2/FiO_2、血清SOD、GSH-Px水平均较治疗前显著上升,且实验组PaO_2/FiO_2、血清SOD、GSH-Px水平明显高于对照组,两组血清MDA水平均较治疗前明显降低,且实验组血清MDA水平显著低于对照组(P0.05)。结论:大承气汤辅助治疗ARDS能够有效改善患者pH、PaO_2/FiO_2,缓解氧化应激状态,利于患者恢复。     

Mesenchymal stem/stromal cells as adjuvant therapy in COVID-19-associated acute lung injury and cytokine storm: Importance of cell identification

Theoretically, mesenchymal stem cells (MSCs) are very promising as adjuvant therapy to alleviate coronavirus disease 2019 (COVID-19)-associated acute lung injury and cytokine storm. Several published studies, which used MSCs to alleviate COVID-19-associated acute lung injury and cytokine storm, reported promising results. However, the evidence came from a case report, case series, and clinical trials with a limited number of participants. Therefore, more studies are needed to get robust proof of MSC beneficial effects.     

一氧化氮在大鼠肢体缺血再灌注后肺损伤中的作用

在大鼠肢体缺血再灌注（LIR）损伤模型上,观察应用一氧化氮合酶（NOS）抑制剂氨基胍（AG）及一氧化氮（NO）合成前体物质L－精氨酸（L－Arg)对大鼠骨骼肌和肺组织的NOS活性、NO含量、丙二醛（MDA）、髓过氧化物酶（MPO）和湿／干重（W／D）值的影响以及肺磷脂酰胆碱（PC）的改变,并观察了肺组织在光镜下形态学的变化。结果显示,与对照组比较,LIR组骨骼肌和肺组织NOS活性均增强,MDA值、MPO活性增加,W／D值增大,肺PC含量降低;光镜下,肺间质多形核粒细胞（PMN）聚集和浸润,肺间隔面密度值增加。给予AG后,与LIR组相比NOS活性降低,NO产生下降,而MPO活性、W／D比值增加,肺PC含量进一步降低;镜下PMN聚集和浸润增加,肺间隔面密度值增大。而给予L－Arg后能 减轻LIR引起的上述变化。上述结果提示,LIR后2h时,骨骼肌和肺组织NOS活性增加,NO产生增多;内源性NO可能在LIR所诱发的早期急性肺损伤中起保护作用。     

肺泡表面活性物质（PS）对盐酸吸入性肺损伤的治疗进展

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,治疗措施包括机械通气及药物综合治疗。肺泡表面活性物质（PS）在维持正常的肺功能起着重要作用,业已证明,PS异常与ALI／ARDS的发病有关,给予外源性PS亦可治疗ALI／ARDS。本文就外源性PS在盐酸吸入性ALI／ARDS的第二时相中的疗效及其可能的作用机制做一综述。     

Increased sTREM-1 plasma concentrations are associated with poor clinical outcomes in patients with COVID-19

Patients with sepsis display increased concentrations of sTREM-1 (soluble Triggering Receptor Expressed on Myeloid cells 1), and a phase II clinical trial focusing on TREM-1 modulation is ongoing. We investigated whether sTREM-1 circulating concentrations are associated with the outcome of patients with coronavirus disease 2019 (COVID-19) to assess the role of this pathway in COVID-19. This observational study was performed in two independent cohorts of patients with COVID-19. Plasma concentrations of sTREM-1 were assessed after ICU admission (pilot cohort) or after COVID-19 diagnosis (validation cohort). Routine laboratory and clinical parameters were collected from electronic patient files. Results showed sTREM-1 plasma concentrations were significantly elevated in patients with COVID-19 (161 [129–196] pg/ml) compared to healthy controls (104 [75–124] pg/ml; P<0.001). Patients with severe COVID-19 needing ICU admission displayed even higher sTREM-1 concentrations compared to less severely ill COVID-19 patients receiving clinical ward-based care (235 [176–319] pg/ml and 195 [139–283] pg/ml, respectively, P = 0.017). In addition, higher sTREM-1 plasma concentrations were observed in patients who did not survive the infection (326 [207–445] pg/ml) compared to survivors (199 [142–278] pg/ml, P<0.001). Survival analyses indicated that patients with higher sTREM-1 concentrations are at higher risk for death (hazard ratio = 3.3, 95%CI: 1.4–7.8). In conclusion, plasma sTREM-1 concentrations are elevated in patients with COVID-19, relate to disease severity, and discriminate between survivors and non-survivors. This suggests that the TREM-1 pathway is involved in the inflammatory reaction and the disease course of COVID-19, and therefore may be considered as a therapeutic target in severely ill patients with COVID-19.     

乌司他丁在急性呼吸窘迫综合征的临床应用研究

目的:观察乌司他丁(UTI)对急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)的临床应用。方法:选择我院ICU自2008年1月至2011年1月收治的160例ARDS患者作为研究对象,采用随机对照的方法,并且经患者或患者家属知情并签字同意分组。分为UTI组(A组)和对照组(B组)。两组均给予相同综合治疗措施,A组除综合治疗外还给予注射用乌司他丁,每次30万U,每日2次。分别记录两组患者开始治疗、治疗后第3天、治疗第7天的生命体征,动脉血气分析、血生化检查结果、并且记录患者在ICU治疗的转归,应用SPSS13.0软件对结果进行统计学分析。结果:经治疗3天A组呼吸频率低于B组,动脉血气分析提示两组PO2、PO2/FiO2、SaO2均有上升。比较后发现A组PO2、PO2/FiO2、SaO2高于B组(P<0.05),两组PO2、SaO2比较有统计学差异。经治疗3天A组与B组生化指标比较、白细胞计数、肾功及血乳酸均有下降,有统计学差异,P<0.05。全部治疗结束后A组与B组死亡率比较(UTI组34.29%,对照组38.26%,P=0.0097)及机械通气时间比较(UTI组7.54±3.27天,对照组11.78±2.69天,P=0.0086),均有统计学差异。结论:大剂量UTI用于ARDS的临床治疗可有效改善患者氧合指数,减少机械通气时间,降低患者的病死率。     

HFOV联合PS对治疗新生儿ALI/ARDS的疗效及对肺动态顺应性的影响

摘要 目的：探讨高频振荡通气（HFOV）联合肺表面活性物质（PS）对治疗新生儿急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）的疗效及对肺动态顺应性的影响。方法：选择2018年1月至2020年12月我院新生儿科收治的160例ALI/ARDS患儿进行研究,按照随机数表法分为观察组和对照组,每组80例。对照组患儿给予常频通气（CMV）模式联合PS治疗,观察组患儿给予HFOV模式联合PS治疗。比较两组患儿一般治疗情况、治疗前后肺动态顺应性、动脉血氧分压（PaO₂）、动脉二氧化氮分压（PaCO₂）、氧合指数（OI）、血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-10的变化,以及治疗期间并发症发生情况。结果：观察组胸片恢复正常时间、机械通气时间、氧暴露时间、ICU停留时间、住院时间结果均明显短于对照组（P＜0.05）,两组患儿病死率相比较,无统计学意义（P＞0.05）;治疗后12 h、24 h、48 h时,观察组肺动态顺应性及PaO₂、OI结果明显高于对照组,PaCO₂明显比对照组低,差异有统计学意义（P＜0.05）;治疗后48 h时,观察组血清TNF-α、IL-6水平均明显低于对照组,IL-10明显比对照组高,差异有统计学意义（P＜0.05）;两组治疗期间,呼吸机相关性肺损伤、颅内出血、气漏、呼吸道感染的总发生率比较,无统计学意义（P＞0.05）。结论：HFOV联合PS治疗新生儿ALI/ARDS疗效明显,可有效改善患儿肺动态顺应性,促进血气分析指标恢复,且可降低炎症因子的表达,值得推广应用。     

Ursodeoxycholic acid protects against lung injury induced by fat embolism syndrome

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life‐threatening disease with a high mortality rate, which was a common complication of fat embolism syndrome (FES). Ursodeoxycholic acid (UDCA) has been reported to exert potent anti‐inflammatory effects under various conditions. In vivo, perinephric fat was injected via tail vein to establish a rat FES model, the anti‐inflammatory effects of UDCA on FES‐induced lung injury were investigated through histological examination, ELISA, qRT‐PCR, Western blot and immunofluorescence. In vitro, human lung microvascular endothelial cells (HPMECs) were employed to understand the protective effects of UDCA. The extent of ALI/ARDS was evaluated and validated by reduced PaO₂/FiO₂ ratios, increased lung wet/dry (W/D) ratios and impaired alveolar‐capillary barrier, up‐regulation of ALI‐related proteins in lung tissues (including myeloperoxidase [MPO], vascular cell adhesion molecule 1 [VCAM‐1], intercellular cell adhesion molecule‐1 [ICAM‐1]), elevated protein concentration and increased proinflammatory cytokines levels (TNF‐α and IL‐1β) in bronchoalveolar lavage fluid (BALF). Pre‐treatment with UDCA remarkably alleviated these pathologic and biochemical changes of FES‐induced ALI/ARDS; our data demonstrated that pre‐treatment with UDCA attenuated the pathologic and biochemical changes of FES‐induced ARDS, which provided a possible preventive therapy for lung injury caused by FES.