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The awake prone position plays an important role in the treatment of hypoxemia and the improvement of respiratory distress symptoms in non-intubated patients. It is widely used in clinical practice because of its simple operation, safety, and economy. To enable clinical medical staff to scientifically and normatively implement prone position for awake patients without intubation, the committees of consensus formulation, guided by evidence-based methodology and Delphi method, conducted literature search, literature quality evaluation and evidence synthesis around seven topics, including indications and contraindications, evaluation, implementation, monitoring and safety management, termination time, complication prevention and health education of awake prone position. After two rounds of expert letter consultation, Expert consensus on implementation strategy of awake prone positioning for non-intubated patients in China (2023) was formulated, and provide guidance for clinical medical staff.
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Humans , Consensus , Prone Position , Wakefulness , China , DyspneaABSTRACT
Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by infection. When an infection occurs, as the first line of defense of the body's immune system, neutrophils are first recruited to the site of infection to capture and kill pathogens by releasing neutrophil elastase (NE). However, a large amount of NE release will injury the surrounding normal tissues and induce organ dysfunction or failure. NE inhibitors can inhibit NE activity and reduce inflammatory response, which may be a promising drug for the treatment of sepsis. Currently, a variety of NE inhibitors have been developed and reported, but there is no systematic overview of their characteristics, and the role and underlying mechanisms of NE and related inhibitors in sepsis have not been thoroughly discussed. This article will make a review in this regard, in order to elucidate the effect of NE and its inhibitors in sepsis.
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Veno-veous extracorporeal membrane oxygenation (VV-ECMO) has been widely used in the treatment for severe acute respiratory distress syndrome (ARDS). Up to now, the routine access to establish VV-ECMO involves two-sites single lumen cannula via femoral vein and internal jugular venous in adult and children, while few studies about the dual lumen cannula (DLC) in VV-ECMO implemented in adult and children have been reported. On December 16, 2021, an unconscious child with severe ARDS due to multiple trauma caused by fatal falling from a height was admitted to Taihe Hospital. The initial diagnosis was hemorrhagic shock, bilateral hemopneumothorax, sternal fracture, cavity organ perforation, splenic rupture, and pelvic fracture and severe ARDS. Despite mechanical ventilation, he progressed to refractory hypoxemia and was treated with VV-ECMO after successful DLC placement in the right internal jugular vein by the mobile ECMO team of intensive care unit of the Union Hospital eventually. In addition, he received endoscopic sputum aspiration, prone position ventilation, anti-infection and nutritional treatment. His oxygenation gradually improved and he was successfully weaned from ECMO after 11 days. In this case, DLC simplified the process without any related complications, suggesting that it can be safely and effectively used in the treatment of Child's severe ARDS.
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Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Most patients with sepsis underwent a state of immune suppression after surviving the acute inflammatory response, and were susceptible to secondary nosocomial infections, leading to a prolonged hospitalization and increased mortality rate. Myeloid-derived suppressor cells (MDSCs), a heterogeneous population with immunosuppressive activities, can contribute to the development of immunosuppression in patients with cancer and inhibit the host immune response, but the characteristics of MDSCs and their functional mechanism has not been fully addressed in the development of sepsis-induced immunosuppression. Thus, this review will summary the new findings on the mechanisms of MDSCs in septic immunosuppressionin order to provide ideas and directions for targeting MDSCs as treatment of septic immunosuppression.
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Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a life support technique for patients with severe respiratory failure. In the past, single lumen cannula was mostly used to constract the vascular pathway of extracorporeal membrane oxygenation. Compared with single-lumen cannula, double lumen cannula (DLC) can reduce recirculation fraction, reduce complications such as infection and bleeding, and facilitate patient's rehabilitation. DLC requires accurate positioning of the catheter. It has been gradually applied in China. This paper will review the key points related to the use of DLC, such as the insertion, position, and complications, etc. to provide guidance for clinical application practice.
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Enteral nutrition plays an irreplaceable role in the nutritional treatment of critically ill patients. In order to help clinical medical staff to manage the common complications during the implementations of enteral nutrition for critically ill patients, the consensus writing team carried out literature retrieval, literature quality evaluation, evidence synthesis. Several topics such as diarrhea, aspiration, high gastric residual volume, abdominal distension, etc. were assessed by evidence-based methodology and Delphi method. After two rounds of expert investigations, Expert consensus on prevention and management of enteral nutrition therapy complications for critically ill patients in China (2021 edition) developed, and provided guidance for clinical medical staff.
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Determining whether patients have volume-responsiveness is one of the frequently asked questions in the intensive care unit, especially in shock patients. Evaluating the volume status and volume responsiveness can help clinical medical staff accurately grasp the patient's cardiac preload, guide reasonable volume management, and help improve patient prognosis. Therefore, many non-invasive and invasive methods have been proposed to evaluate volume responsiveness. Inferior vena cava ultrasound has been widely used to guide the fluid management of critically ill patients due to its simplicity, non-invasiveness, and good repeatability. This article reviews the clinical applications of inferior vena cava ultrasound in fluid management of critically ill patients, so as to provide a reference for circulatory management of critically ill patients.
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<p><b>Objective</b>Mechanical ventilation (MV) has long been used as a life-sustaining approach for several decades. However, researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly, which is termed as ventilator-induced lung injury (VILI). This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.</p><p><b>Data Sources</b>This review was based on articles in the PubMed database up to December 2017 using the following keywords: "ventilator-induced lung injury", "pathogenesis", "mechanism", and "biotrauma".</p><p><b>Study Selection</b>Original articles and reviews pertaining to mechanisms of VILI were included and reviewed.</p><p><b>Results</b>The pathogenesis of VILI was defined gradually, from traditional pathological mechanisms (barotrauma, volutrauma, and atelectrauma) to biotrauma. High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas, volutrauma, and atelectrauma. In the past two decades, accumulating evidence have addressed the importance of biotrauma during VILI, the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release, reactive oxygen species production, complement activation as well as mechanotransduction.</p><p><b>Conclusions</b>Barotrauma, volutrauma, atelectrauma, and biotrauma contribute to VILI, and the molecular mechanisms are being clarified gradually. More studies are warranted to figure out how to minimize lung injury induced by MV.</p>
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Animals , Humans , Barotrauma , Metabolism , Reactive Oxygen Species , Metabolism , Ventilator-Induced Lung Injury , Metabolism , Wounds and Injuries , MetabolismABSTRACT
<p><b>Background</b>Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis. Protectin DX (PDX), a pro-resolving lipid mediator, exhibits protective effects in ALI. Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide (LPS).</p><p><b>Methods</b>BALB/c mice were randomly divided into five groups: sham, LPS, LPS plus 1 ng of PDX (LPS + PDX-1 ng), LPS plus 10 ng of PDX (LPS + PDX-10 ng), and LPS plus 100 ng of PDX (LPS + PDX-100 ng). Bronchoalveolar lavage fluids (BALFs) were collected after 24 h, and total cells, polymorphonuclear leukocytes, monocyte-macrophages, and lymphocytes in BALF were enumerated. The concentration of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein (MIP)-1α, and MIP-2 in BALF was determined, and histopathological changes of the lung were observed. The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema. After determining the optimal dose of PDX, neutrophil-platelet interactions in whole blood were evaluated by flow cytometry.</p><p><b>Results</b>The highest dose of PDX (100 ng/mouse) failed to provide pulmonary protective effects, whereas lower doses of PDX (1 ng/mouse and 10 ng/mouse), especially 1 ng PDX, alleviated pulmonary histopathological changes, mitigated LPS-induced ALI and pulmonary edema, inhibited neutrophil infiltration, and reduced pro-inflammatory mediator (IL-1β, IL-6, TNF-α, and MIP-1α) levels. Meanwhile, 1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-10 levels. The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI.</p><p><b>Conclusion</b>PDX exerts protective effects in LPS-induced ALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.</p>
Subject(s)
Animals , Male , Mice , Acute Lung Injury , Drug Therapy , Chemokine CXCL2 , Metabolism , Docosahexaenoic Acids , Therapeutic Uses , Flow Cytometry , Interleukin-10 , Metabolism , Interleukin-1beta , Metabolism , Interleukin-6 , Metabolism , Lipopolysaccharides , Toxicity , Lung , Metabolism , Mice, Inbred BALB C , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
<p><b>Objective</b>Exposure to halogens, such as chlorine or bromine, results in environmental and occupational hazard to the lung and other organs. Chlorine is highly toxic by inhalation, leading to dyspnea, hypoxemia, airway obstruction, pneumonitis, pulmonary edema, and acute respiratory distress syndrome (ARDS). Although bromine is less reactive and oxidative than chlorine, inhalation also results in bronchospasm, airway hyperresponsiveness, ARDS, and even death. Both halogens have been shown to damage the systemic circulation and result in cardiac injury as well. There is no specific antidote for these injuries since the mechanisms are largely unknown.</p><p><b>Data Sources</b>This review was based on articles published in PubMed databases up to January, 2018, with the following keywords: "chlorine," "bromine," "lung injury," and "ARDS."</p><p><b>Study Selection</b>The original articles and reviews including the topics were the primary references.</p><p><b>Results</b>Based on animal studies, it is found that inhaled chlorine will form chlorine-derived oxidative products that mediate postexposure toxicity; thus, potential treatments will target the oxidative stress and inflammation induced by chlorine. Antioxidants, cAMP-elevating agents, anti-inflammatory agents, nitric oxide-modulating agents, and high-molecular-weight hyaluronan have shown promising effects in treating acute chlorine injury. Elevated free heme level is involved in acute lung injury caused by bromine inhalation. Hemopexin, a heme-scavenging protein, when administered postexposure, decreases lung injury and improves survival.</p><p><b>Conclusions</b>At present, there is an urgent need for additional research to develop specific therapies that target the basic mechanisms by which halogens damage the lungs and systemic organs.</p>
Subject(s)
Animals , Humans , Acute Lung Injury , Chlorine , Toxicity , Halogens , Toxicity , Lung , Pathology , Respiratory Distress Syndrome , Drug TherapyABSTRACT
Objective To investigate the effect of exogenous protectin DX (PDX) on acute lung injury in septic mice.Methods Thirty male C57BL/6 mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 3 groups (n =10 each) using a random number table:sham operation group (Sham group),sepsis group (S group) and PDX group.Sepsis was produced by cecum ligation and puncture (CLP) in the mice anesthetized with pentobarbital sodium.At 1 h after CLP,PDX 300 ng was injected intraperitoneally in PDX group,and the equal volume of normal saline was given in Sham and S groups.At 24 h after CLP,the mice were sacrificed,and the broncho-alveolar lavage fluid (BALF) was collected for determination of interleukin-1beta (IL-1β),tumor necrosis factor-alpha (TNF-α),IL-6 and IL-10 concentrations,and the lungs were removed for microscopic examination and for determination of the myeloperoxidase (MPO) activity,wet/dry lung weight ratio (W/D ratio) and phosphorylation of nuclear factor-kappa B (NF-κB) p65.Lung injury scores were calculated.Results Compared with Sham group,the lung injury score,MPO activity,W/D ratio,phosphorylation of NF-κB p65,and concentrations of protein and inflammatory factors in BALF were significantly increased in S and PDX groups (P＜0.05).Compared with S group,the lung injury score,MPO activity,W/D ratio,phosphorylation of NF-κB p65,and concentrations of protein,IL-1β,TNF-α and IL-6 in BALF were significantly decreased,and the concentration of IL-10 in BALF was significantly increased in PDX group (P＜0.05).Conclusion Exogenous PDX can alleviate acute lung injury through inhibiting NF-κB activity in the lung tissues of septic mice.
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Mechanical ventilation is not only an important treatment method of acute respiratory distress syndrome (ARDS),but also one of the basic treatments in the intensive care unit (ICU).However,mechanical ventilation itself can cause or aggravate acute lung injury,which is called ventilator-induced lung injury (VILI).Currently,clinical pathogenesis of VILI includes four categories such as barotrauma,volutrauma,atelectrauma and hiotrauma.The pathogenesis of mechanical injury has been widely accepted,but the biological injury pathogenesis is unclear.With further research,we found that in the late stage VILI patients occured proliferation of puhnonary fibrosis,which may be formed by partial epithelial-mesenchymal transdifferentiation (EMT).Further study of specific pathogenesis of biotrauma and ARDS pulmonary fibrosis proliferation could provide new ideas for the clinical treatment of VILI.
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Acute respiratory distress syndrome (ARDS) patients experiencing protective mechanical ventilation, is associated with a marked mortality reduction. However, the incidence of acute cor pulmonale (ACP) in ARDS patients has recently been reported to range between 22% and 25%, as well as a trend for higher mortality. Therefore, the mechanical ventilation strategy is proposed, not only based on the protection of the lung, but also focused on the impact on the right ventricle function. Currently, point-of-care ultrasound has been widely practiced in a variety of clinical setting, which plays more and more important role in the early detection and management of ARDS and its complications. A retrospective study concerning the incidence, pathophysiology and risk factors for ACP patients in ARDS was done to analysis the application of lung ultrasound and echocardiography combined with lung ultrasound in clinical hemodynamics monitoring, and so as to optimize the ventilation setting to protect the function of lung and right ventricle. Further exploration of effective improvement of the pulmonary vascular and right ventricle function the goal-directed ultrasound approach, and the diagnosis and treatment flow is expected.
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Objective To evaluate the effects of rosiglitazone on ventilator-associated lung injury (VALI) in mice.Methods Twenty-four healthy male C57 mice,weighing 20-25 g,aged 6-8 weeks,were randomly divided into 3 groups (n =8 each) using a random number table:sham operation group (group S);group VALI;rosiglitazone group (group RGZ).The mice only underwent tracheotomy in group S.In group VALI,the mice were ventilated (respiratory rate 80 breaths/min,duration 4 h,tidal volume 40 ml/kg,fraction of inspired oxygen 21％,inspiratory/expiratory ratio 1:2,PEEP 0).In group RGZ,30 mg/kg rosiglitazone was given orally at 30 min before ventilation,and the other treatments were similar to those previously described in group VALI.At the end of ventilation,the mice were sacrificed,and the left lung was lavaged,and the broncho-alveolar lavage fluid (BALF) was collected for determination of neutrophil count.The pulmonary specimens were collected from the upper lobe of right lungs for microscopic examination of the pathological changes which were scored.The pulmonary specimens were obtained from the middle lobe of right lungs for measurement of the contents of interleukin-lbeta (IL-1β),tumor necrosis factor-alpha (TNF-α),high mobility group box-1 (HMGB-1) and receptor for advanced glycation end-products (RAGE) by enzyme-linked immunosorbent assay.Results Compared with group S,the neutrophil counts in BALF,contents of IL-1β,TNF-α,HMGB1 and RAGE,and lung injury score were significantly increased in VALI group (P＜0.01),and no significant change was found in the parameters mentioned above in group RGZ (P＞0.05).Compared with group VALI,the neutrophil counts in BALF,contents of IL-1β,TNF-α,HMGB1 and RAGE,and lung injury score were significantly decreased in group RGZ (P＜0.01).Conclusion Rosiglitazone can mitigate VALI in mice.
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Objective To evaluate the effect of BML?111 on ventilator?induced lung injury in rats. Methods Forty?eight healthy male Sprague?Dawley rats, weighing 200-250 g, aged 6-8 weeks, were randomized into 6 groups ( n=8 each) using a random number table: control group ( C group) , low tidal volume (VT) group (LVTgroup), high VT group (HVTgroup), low dose BML?111 group (BL group), high dose BML?111 group ( BH group) , and BML?111 plus BOC?2 ( lipoxin A4 receptor antagonist) group ( BOC?2 group) . Group C kept spontaneous breathing after tracheotomy, and received no mechanical venti?lation. The rats in the other 5 groups were mechanically ventilated ( respiratory rate 80 breaths∕min, frac? tion of inspired oxygen 21%, positive end?expiratory pressure 0) . The VT was 6 ml∕kg in group LVT , or 20 ml∕kg in HVT, BL, BH and BOC?2 groups. BML?111 0?1 and 1?0 mg∕kg were injected intraperitoneally during ventilation in BL and BH groups, respectively. In group BOC?2, BOC?2 50 μg∕kg was injected in?traperitoneally before ventilation, and BML?111 1?0 mg∕kg was injected intraperitoneally during ventilation. Arterial blood samples were collected at 4 h of ventilation, arterial oxygen partial pressure ( PaO2 ) was de?termined. Then animals were sacrificed by exsanguination. Bronchoalveolar lavage fluid ( BALF) of the left lung was collected for determination of neutrophil count, and the level of neutrophil was calculated. The right lung tissue specimens were obtained for microscopic examination, and for determination of wet∕dry lung weight ratio ( W∕D ratio ) , myeloperoxidase ( MPO ) activity, and contents of malondialdehyde ( MDA) , monocyte chemoattractant protein?1 ( MCP?1) , tumor necrosis factor?alpha ( TNF?α) , interleu?kin?1beta ( IL?1β) and IL?6. Results Compared with group C, PaO2 was significantly decreased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were increased in group HVT ( P0?05) . Compared with group HVT , PaO2 was significantly increased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were decreased in group BH, and the contents of TNF?α, IL?1βand IL?6 were significantly decreased ( P0?05) . Compared with group BH, PaO2 was significantly decreased, and the level of neutrophil in BALF, W∕D ratio, MPO activity, and contents of MDA, MCP?1, TNF?α, IL?1β and IL?6 were increased in group BOC?2 (P<0?05). The pathological changes were significantly attenuated in group BL as compared with HVT and BOC?2 groups. Conclusion BML?111 can attenuate ventilator?induced lung injury in rats, and activated lipoxin A4 receptors are involved in the mechanism.
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ObjectiveTo investigate the effect of sivelestat sodium on the prognosis in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS).Methods Databases including PubMed, EBSCO, Springer, Ovid, Wanfang data, CNKI and China Biology Medicine (CBM) were searched to identify randomized controlled trials (RCTs) regarding sivelestat sodium treatment for ALI/ARDS published from 1985 to December 2014. The patients in treatment group received intravenous infusion of sivelestat sodium, and those in control group received normal saline. The items for analysis were 28-day mortality, duration of mechanical ventilation, length of intensive care unit (ICU) stay, and oxygenation index on day 3. According to the evaluation method of Cochrane system, data extraction and quality assessment from the literature were carried out. Meta-analysis was performed using RevMan 5.3. The publication bias was analyzed with funnel plot.Results Five RCTs with a total of 780 participants were included, with 389 patients in sivelestat sodium group, and 391 in control group. Meta analysis showed: compared with control group, sivelestat sodium could not lower the 28-day mortality [odds ratio (OR) = 0.91, 95% confidence interval (95%CI) =0.66-1.26,P = 0.58], or shorten the duration of mechanical ventilation or length of ICU stay [duration of mechanical ventilation: mean difference (MD) = -0.02, 95%CI = -0.29 to 0.24,P = 0.87; length of ICU stay:MD = -9.63, 95%CI =-23.34 to 4.08,P = 0.17], but it could improve oxygenation index on day 3 (MD = 0.88, 95%CI = 0.39 to 1.36, P = 0.000 4). Heterogeneity was not significant for the main analysis and no publication bias was shown on funnel plot. Conclusion Sivelestat sodium gave rise to a better oxygenation on day 3, but did not change the length of mechanical ventilation and ICU stay, and it did not improve 28-day mortality in ALI and ARDS.
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Objective To compare the hypnotic effects of propofol administered by target-controlled infusion (TCI in daytime and nighttime,in order to explore the effect of circadian rhythm on the sedative effect of propofol.Methods Sixty-five male ASA Ⅰ or Ⅱ patients,aged 18-55 years,with the body mass index (BMI) of 18.5-24.9 kg/m2,undergoing emergency minor hand surgery were divided into two groups according to the time of the day when they received TCI of propofol:daytime group (from 07:01 to 19:00) and nighttime group (from 19:01 to 07:00).The pharmacokinetic parameters proposed by Schnider et al.which suggested the effect-site concentration (Ce) was used.Four Ces of propofol were set at 0.8,1.2,2.0 and 4.0 μg/ml,respectively.Ce was increased step by step and each Ce was maintained for 5 minutes.The level of sedation at each Ce was assessed by bispectral index (BIS) and observer's assessment of alertness/sedation (OAA/S) scores.BIS values and Ces of propofol were recorded and compared between the two groups when the patients lost consciousness (OAA/S score =2).Results There were 28 and 30 patients in daytime and nighttime groups,respectively.When Ces were 1.2 and 2.0 μg/ml,the BIS values were significantly lower in the nighttime group than in the daytime group.There was no significant difference in BIS values between the two groups when Ces were 0.8 and 4.0 μg/ml.When the patients lost consciousness (OAA/S =2),the BIS value was comparable between the two groups,but Ce was significantly lower in the nighttime group than in the daytime group.Conclusion The hypnotic effect of propofol is greater during night time than during day time.
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Objective To evaluate the effect of BML-111 on NF-κB pathway during acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two adult male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 4 groups (n =8 each) using a random number table:sham operation group (group S),hemorrhagic shock and resuscitation group (group HSR),BML-111 group,and BML-111 + BOC-2 (lipoxin A4 receptor antagonist) group (group BOC-2).The animals were anesthetized with intraperitoneal pentobarbital sodium.Hemorrhagic shock was induced by blood letting and maintained for 30 min.The animals were then resuscitated for 30 min by infusion of the shed blood and lactated Ringer's solution.In group BOC-2,BOC-2 (50 μg/kg) was injected intraperitoneally before blood letting.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.The rats were sacrificed at 2 h after the end of resuscitation and lungs were removed for determination of pathological changes,myeloperoxidase (MPO) activity,intercellular adhesion molecule-1 (ICAM-1) expression (by immunohistochemistry),tumor necrosis factor-alpha (TNF-α) content (by ELISA),and NF-κB p65 and IκB-α expression (by Western blot).Results Compared with group S,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and IκB-α expression was down-regulated in group HSR.Compared with group.HSR,the MPO activity,ICAM-1 expression,and TNF-α content were significantly decreased,NF-κB p65 expression was down-regulated,IκB-α expression was up-regulated,and pathological changes of lung were attenuated in group BML-111.Compared with group BML-111,the MPO activity,ICAM-1 expression,and TNF-α content were significantly increased,NF-κB p65 expression was up-regulated,and lκ:B-α expression was down-regulated,and pathological changes of lung were aggravated in group BOC-2.Conclusion BML-1 11 inhibits activation of NF-κB pathway and inflammatory responses,thus mitigating acute lung injury induced by hemorrhagic shock and resuscitation in rats.
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Objective To evaluate the effect of lipoxin A4 receptor agonist BML-111 on acute lung injury induced by hemorrhagic shock and resuscitation in rats.Methods Thirty-two healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-250 g,were randomized into 4 groups (n =8 each) using a random number table:sham operation group (S group),hemorrhagic shock/resuscitation group (HSR group),BML-111 group,and BML-111 plus BOC-2 (lipoxin A4 receptor antagonist) group (BOC-2 group).The animals were anesthetized with 2％ pentobarbital sodium 80 mg/kg,tracheostomized and mechanically ventilated.Left common carotid artery was cannulated for blood-letting and fluid infusion.Hemorrhagic shock was induced according to the method described by Kochanek et al.MAP was reduced to 35-45 mmHg and maintained at this level for 30 min.The animals were then resuscitated for 30 min with infusion of the blood withdrawn and lactated Ringer' s solution 2 times the volume of blood withdrawn.In BML-111 and BOC-2 groups,BML-111 (1 mg/kg) was injected intraperitoneally at the beginning of resuscitation.In BOC-2 group,BOC-2 (50 μg/kg) was injected intraperitoneally before blood-letting.The rats were sacrificed at 2 h after completion of resuscitation.Bronchoalveolar lavage fluid (BALF) was collected for determination of neutrophil count.Lungs were excised for microscopic examination of the pathological changes and for determination of wet/dry lung weight ratio (W/D ratio),contents of interleukin-1 (IL-1β) and IL-6,and phosphorylation of mitogen-activated protein kinase (MAPK).Results Compared with group S,the neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly increased in HSR group (P ＜ 0.05).The neutrophil count in BALF,W/D ratio,contents of IL-1β and IL-6,and phosphorylation of MAPK were significantly lower in BML-111 group than in HSR group,and higher in BOC-2 group than in BML-111 group (P ＜ 0.05).Conclusion BML-111 can attenuate acute lung injury induced by hemorrhagic shock and resuscitation in rats and inhibition of activation of MAPK pathways and reduction of inflammatory responses in lung tissues are involved in the mechanism.
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Objective To evaluate the effects of aspirin-triggered lipoxin A4 (ATL) on lipopolysaccharide (LPS)-induced acute lung injury in mice.Methods Thirty male SPF BALB/C mice,aged 10-12 weeks,weighing 25-30 g,were randomly assigned into 3 groups (n =10 each):normal saline group (group NS),LPS group and ATL groups.ATL 0.1 ml was injected via the tail vein 1 h after intra-tracheal instillation of 3 mg/kg LPS in LPS group.In ATL group,ATL 0.2 mg/kg was injected via the tail vein 1 h after intra-tracheal instillation of 3 mg/kg LPS.At 24 h after instillation,the mice were sacrificed.Bronchoalveolar lavage fluid was collected for determination of the total cell count,proportion of the polymorphonuclear leukocytes,proportion of the mononuclear leukocytes,and concentrations of the total protein,TNF-αt,IL-6,monocyte chemoattractant protein-1 (MCP-1) and IL-10.Lungs were removed for determination of myeloperoxidase (MPO) activity,phosphorylation of p38 mitogenactivated protein kinase (p38 MAPK),c-Jun N-terminal kinase (JNK),and extracellular signal-regulated kinase 1/2 (ERK1/2) in lung tissues and for microscopic examination.The pathological changes of lungs were scored.Results Compared with NS group,the lung injury scores,total cell counts,proportion of polymorphonuclear leukocytes,and concentrations of TNF-α,IL-6 and MCP-1 were significantly increased,and the proportion of mononuclear leukocytes was decreased in LPS and ATL groups,and IL-10 concentrations were decreased,and the concentrations of the total protein,MPO activity,and phosphorylation of p38 MAPK,JNK and ERK1/2 were significantly increased in group LPS (P ＜ 0.05),and no significant change in the concentrations of the total protein,MPO activity,phosphorylation of p38 MAPK,JNK and ERK1/2 was found in group ATL (P ＞ 0.05).Compared with LPS group,the lung injury scores,total cell counts,proportion of polymorphonuclear leukocytes and the concentrations of the total protein,TNF-α,IL-6 and MCP-1 were significandy decreased,the proportion of mononuclear leukocytes and IL-10 concentration were increased,and MPO activity and phosphorylation of p38 MAPK and JNK were decreased (P ＜ 0.05),and no significant change in the phosphorylation of ERK1/2 was found in group ATL (P ＞ 0.05).Conclusion ATL can ameliorate LPS-induced acute lung injury by inhibiting activations of p38MAPK and JNK signal pathways in mice.