Role of the coagulation and fibrinolysis in acute lung injury

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common, life-threatening causes of acute respiratory failure that arise from a variety of local and systemic insults. The pathogenesis of ALI/ARDS is complicated and not yet completely interpreted today. The role of altered coagulation and fibrinolysis in the pathogenesis of ALI/ARDS has been investigated. This review will summarize the current understanding of coagulation and fibrinolysis in human ALI/ARDS with emphasis on pathways that could be potential therapeutic targets. These pathways include the tissue factor pathway, the protein C pathway and modulation of fibrinolysis via plasminogen activator inhibitor-1.     

Paracrine effect of stem cells on treatment of acute lung injury/acute respiratory distress syndrome

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent the leading cause of morbidity and mortality in critical patients. Despite improvements in supportive care and mechanical ventilation, recent data indicate that the mortality of ALI/ARDS is still high. Cell-based therapy with stem cells is an attractive new therapeutic approach. Stem cells have the capacity to secrete multiple paracrine factors that can regulate inflammation, improve alveolar fluid clearance, regulate endothelial and epithelial permeability, enhance tissue repair via chemotaxis and inhibit bacterial growth. This review focuses on the recent studies, which support the potential therapeutic use of stem cells in ALI/ARDS with an emphasis on the role of paracrine soluble factors.     

Present strategies and future perspectives for therapies of ALI/ARDS

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), the complicated and devastating illness, resulted from various processes of systemic inflammatory response syndrome (SIRS), injure directly or indirectly the lung. With the advance of investigations in SIRS and multiple organs disfunction syndrome (MODS), inflammation development and control have been considered to be the important mechanism of ALI/ARDS. The research hotspot is also focused on the inflammatory cells and cytokines. Dachengqi decoction can influence on the functions of inflammatory cells and cytokines, so the strategies of anti-inflammatory treatment on immunoregulation became the key point for prevention and treatment of ALI/ARDS with traditional Chinese medicine.     

Vinpocetine injection attenuates lipopolysaccharide-induced acute lung injury in rats

AIM:To observe the inhibitory effects of vinpocetine injection on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in the rats and to explore the underlying mechanisms.METHODS:Male Wistar rats (n=50) were randomly divided into 5 groups:control group,ALI model group,and low,medium and high doses of vinpocetine treatment groups.The rats in control group were injected with 0.9% NaCl at 5 mL/kg through femoral vein.The rats in ALI model group received LPS at 10 mg/kg through femoral vein.After injected with LPS,the rats in vinpocetine treatment groups received vinpocetine at 0.2 mg/kg,0.7 mg/kg or 1.2 mg/kg via intraperitoneal injection.The pathological changes of the lung tissues were observed under microscope with HE staining.The cell apoptosis in the lung tissues was detected by TUNEL staining.Myeloperoxidase (MPO) activity was measured by the method of spectrophotometry.The protein expression of NF-κB,ICAM-1,VCAM-1,Bax and Bcl-2 was determined by Western blot.RESULTS:Compared with ALI group,administration of vinpocetine significantly attenuated the structural injury of the lung and the infiltration of inflammatory cells.Moreover,vinpocetine decreased cell apoptosis and MPO activity in the lung tissues of ALI rats.In addition,the protein expression of NF-κB,ICAM-1,VCAM-1 and Bax was inhibited after vinpocetin treatment,whereas Bcl-2 expression was increased.CONCLUSION:Vinpocetine attenuates LPS-lung injury by reducing MPO activity and regulating NF-κB,ICAM-1,VCAM-1,Bax and Bcl-2 protein expression.     

Effects of bilirubin on oxygen free radicals and caspase-3 in acute lung injury rats

AIM:To investigate the mechanisms by which bilirubin inhibits acute lung injury (ALI). METHODS:30 female Wistar rats were divided into normal group, ALI group and bilirubin treatment group. ALI was induced by intravenous injection of LPS. The contents of OH^-, H₂O₂ and O₂^· in the lung as well as the expression of caspase-3 in the lungs were investigated. RESULTS:(1) The contents of OH^-, H₂O₂ and O₂^· in the lung homogenate and the expression of caspase-3 in the lungs in ALI group increased compared with those in normal group (P<0.05). (2) The contents of OH^-, H₂O₂ and O₂^· in the lung homogenate and the expression of caspase-3 in the lungs in bilirubin treatment group increased compared with those in normal group, but decreased compared with those in ALI models (P<0.05). CONCLUSION:(1) Bilirubin was shown to be able to ameliorate apoptosis in ALI rats. (2) The increase in the contents of OH^-, H₂O₂, O₂^· in ALI group indicated the development of oxidative lung injury, which was ameliorated by bilirubin. (3) Expression of caspase-3 confirmed that the model made by LPS was associated with apoptosis, which was reduced by bilirubin.     

Role of p38 MAPK-HSP27 signaling pathway in rat acute lung injury induced by lipopolysaccharide

AIM: To observe the role of p38 mitogen-activated protein kinase (p38 MAPK)-heat-shock protein 27 (HSP27) signaling pathway in lipopolysaccharide-induced acute lung injury (ALI) in rats. METHODS: Wistar rats were randomly divided into control group, ALI group and ALI+SB203580 group. After the experimental model was established, the rats were sacrificed. The pathological changes of the lung and the changes of F-actin and G-actin in the endothelial cells were observed. The ratio of wet weight to dry weight (W/D) of the lung tissues was measured. The protein levels in bronchoalveolar lavage fluid (BALF) were detected. The levels of IL-6 and TNF-α in serum and BALF were tested. The concentrations of p-p38 and p-HSP27 in the lung were determined. RESULTS: In ALI group, the protein levels in BALF and W/D ratio of the lung increased significantly at 2 h. The levels of TNF-α and IL-6 in serum and BALF began to increase at 2 h, which had significant difference as compared with control group. Aleolar epithelial swelling, alveolar walls widening, alveolar interstitial and cavity edema, and the exudation of alveolar inflammation cells, red blood cells and protein were observed in ALI group. The protein levels in BALF and W/D ratio of the lung in ALI+SB203580 group were much less than those in ALI group. The exudation of alveolar inflammation cells, red blood cells and protein, and the interstitial and alveolar edema in ALI+SB203580 group alleviated as compared with ALI group. The expression of p-p38 MAPK and p-HSP27 in the lung at 2 h in ALI group was higher than that in control group. F-actin expression in ALI group obviously increased than that in control group at time points of 0 h and 8 h. Compared with ALI group, the expression of p-HSP27 and F-actin in ALI+SB203580 group was reduced. CONCLUSION: Lipopolysaccharide activates p38 MAPK-HSP27 signaling pathway and induces lung injury. Blockage of p38 MAPK-HSP27 signaling pathway may reduce lung injury.     

Pre-treatment with melatonin inhibits oleic acid-induced acute lung injury in rats

AIM: To assess the protective role of melatonin (MEL) in a rat model of oleic-induced acute lung injury.METHODS: Twenty-four rats were randomly allocated to three groups as follows: saline(NS) injection group, oleic acid(OA) injection group and MEL plus OA injection group, the lavage protein, lung wet-to-dry weight ratio, malondialdehyde(MDA) content, superoxide dismutase(SOD) activity and lung histopathology were examined. RESULTS: (1) Injection 0.15 mL/kg of OA led to a severe acute lung injury(ALI), characterized by significantly increasing in lavage protein, lung coefficient (P<0.01), and by histopathological alterations which presented hemorrhage, edema, thickened alveolar septum and the existence of inflammatory cells in alveolar spaces; (2) Infusion of MEL (20 mg/kg, intraperitoneally for 60 min before the oleic acid) markedly alleviated above-mentioned symptom induced by OA, consistent with decrease of MDA level (P<0.01) and the increase of SOD activty (P<0.01). CONCLUSION: Pre-treatment with MEL can attenuate the OA-induced ALI in rats via cleaning and preventing the formation of free radicals and further lessening the increase of alveolocapillary membrane permeability, these data suggest that MEL may be effective in the prevention of ALI.     

Expression of intercellular adhesion molecule in lung tissues of experimental acute lung injury and the effect of rhubarb

AIM:To approach the relationship between the expression of intercellular adhesion (ICAM-1 mRNA) and acute lung injury (ALI) as well as the mechanisms of rhubarb in the prevention and treatment of the lung injury. METHODS:ALI animal model was performed by Lipopolysaccharide (LPS). The rats were divided into 4 groups: LPS group, control group, rhubarb+LPS group and dexamethasone+LPS group. Histopathological examination and biological markers were measured for the lung specimens. Molecular hybridization method was used to determine the expression of ICAM-1 mRNA. RESULTS:The ICAM-1 mRNA expression in the lung tissues of LPS group significantly increased compared with control group (P＜0.01), rhubarb and dexamethasone had the action of decreasing the ICAM-1 mRNA expression (P＜0.05, P＜0.01); pathologic changes and the biological markers of ALI significantly decreased or ameliorated. CONCLUSION:The increase in the expression of ICAM-1 mRNA in the lung tissues of ALI is involved in the formation of ALI. Rhubarb and dexamethasone can ameliorate the lung damage, mechanism of which may be related to the inhibition of ICAM-1 mRNA expression.     

Effects of neutrophil extracellular traps on acute lung injury in neonatal rats

AIMTo investigate the role of neutrophil extracellular traps (NETs) in neonatal rats with acute lung injury (ALI). METHODSThirty 7-day-old SD rats were randomly divided into normal saline control group, ALI group and ALI+deoxyribonuclease (Dnase) group (each n=10). The rats in ALI group were intraperitoneally injected with lipopolysaccharides (LPS) at 20 mg/kg, and the rats in ALI+Dnase group were intraperitoneally injected with Dnase at 5 mg/kg after LPS injection. After 6 h, the rats were anesthetized with chloral hydrate, bronchial alveolar lavage fluid (BALF) was collected, and the content of cell-free DNA (cf-DNA) in BALF was detected by fluorescence microarray. The right lung tissues were fixed in 4% paraformaldehyde, and the morphological structure of the lung tissues were observed by HE staining. The content of interleukin-6 (IL-6) and tumor necrosis factor-α （TNF-α） in the left lung homogenate was measured by ELISA. Immunofluorescence and Western blot were used to detect the production of citrullinated histone H3 (CitH3) and myeloperoxidase (MPO) in the rat lung tissues. RESULTSCompared with control group, the levels of cf-DNA, CitH3, MPO, IL-6 and TNF-α in lung tissues of neonatal rats in ALI group and ALI+Dnase group were all increased (P<0.05), and severe inflammatory infiltration in the lung tissues was observed. Compared with ALI group, the levels of cf-DNA, CitH3, MPO, IL-6 and TNF-α in ALI+Dnase group were decreased (P<0.05), and the inflammatory infiltration was attenuated. CONCLUSION In neonatal rats with ALI, the level of NETs is an important indicator of lung tissue injury, and NETs may be a new target for the treatment of neonatal ALI.     

Protective effect of Auricularia auricular-judae polysaccharide on pulmonary tissues of rats with LPS-induced acute lung injury

AIM: To investigate the effects of Auricularia auricular-judae polysaccharide(AAP) on pulmonary tissues of rats with LPS-induced acute lung injury(ALI) and its mechanisms.METHODS: Adult Sprague-Dawley rats were randomly divided into control group, LPS group,low-dose AAP group, middle-dose AAP group, high-dose APP group, and dexamethasone group. The rats were injected with LPS(8 mg/kg, ip) to induce ALI. The rats in the AAP groups were treated with AAP for 7 d before the induction of ALI. The protein concentration in the bronchoalveolar lavage fluid(BALF) was measured. The lung edema degree was measured by detecting the wet/dry weight ratio. The myeloper-oxidase(MPO), total antioxidant capacity(T-AOC), total superoxide dismutase(T-SOD), nitric oxide synthase(NOS) and malondialdehyde(MDA) levels were determined. The pathological changes of the lung tissues were evaluated by HE staining.RESULTS: Treatment with AAP significantly improved LPS-induced lung pathological changes, attenuated the protein concentration in the BALF and wet/dry weight ratio, inhibited the activities of MPO and NOS, reduced MDA level and increased the activities of T-AOC and T-SOD.CONCLUSION: AAP protects against LPS-induced acute lung injury in rats.     

Sphingosine-1-phosphate receptor-2 attenuates lipopolysaccharide-induced acute lung injury

AIM: To investigate the effects and mechanisms of sphingosine-1-phosphate receptor-2 (S1P2R)on lipopolysaccharide (LPS)-induced acute lung injury (ALI). METHODS: ALI model was induced by intratracheal administration of LPS in both wild-type mice and S1P2R -deficient mice. The pathological changes in the lung tissues were observed, and the protein concentration, total cell number, neutrophil ratio, TNF-α level and IL-6 level were determined in the bronchoalveolar lavage fluid (BALF) 24 h after LPS injection. In order to investigate the mechanisms of S1P2R in LPS-induced ALI, 10 min before LPS injection, both wild-type mice and S1P2R -deficient mice were injected with nitric oxide synthase inhibitor by tail vein injection, the pathological changes of the lung tissues were observed, and the protein concentration and total cell number in BALF were determined 12 h after LPS injection. RESULTS: Compared with wild-type mice, S1P2R -deficient mice showed more severe LPS-induced ALI, and the protein concentration, neutrophils and inflammatory cytokines in BALF were significantly increased in S1P2R -deficient mice. Administration of nitric oxide synthase inhibitor N^ω-L-nitro-arginine methyl ester protected S1P2R -deficient mice from aggravation of ALI. CONCLUSION: S1P2R mediates the protection from LPS-induced ALI possibly through inhibiting nitric oxide synthase.     

Colquhounia root tablet inhibits the expression of adhesion molecule in acute lung injury of rats

AIM: To study the effects of colquhounia root tablet on the expression of adhesion molecule in acute lung injury of rats.METHODS: The rats were divided into 3 groups: ALI group,colquhounia root tablet＋ALI group and control group .ALI animal model was performed by treatment with oleic acid.The positive expression rates of CD11a,CD11b and CD18 in polymorphonuclear neutrophils and monocytes were analyzed by flow cytometry.ICAM-1 expression in lung tissue was determined by immunohistochemistry,histopathological examination and biological markers were measured from lung specimens.RESULTS: Colquhounia root tablet decreased the expression of CD11a,CD11b and CD18 in polymorphonuclear neutrophils and monocytes,and ICAM-1 in lung tissue (P<0.01),pathologic changes and the biological markers of ALI significantly ameliorated.CONCLUSION: The increase in the expression of CD11a/CD18 and CD11b/CD18 in polymorphonuclear neutrophils and monocytes,and expression of ICAM-1 in lung tissues of ALI may be involved in the formation of ALI.Colquhounia root tablet effectively ameliorates the lung damage,mechanism of which may be related to inhibition of adhesion molecule expression.     

Changes of pulmonary apoptosis and NOS mRNA in the lipopolysaccharide-induced acute lung injury

AIM: To observe the chronological changes of pulmonary apoptosis and the expression of iNOS mRNA,nNOS mRNA and eNOS mRNA in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to investigate the mechanisms of ALI.METHODS: Rats were randomly divided into 2 groups: control group and LPS treated group.The rats were injected with either saline or LPS and killed at 1,3,6,9 and 12 h after LPS injection.The expressions of iNOS mRNA,nNOS mRNA and eNOS mRNA in the lung tissue were respectively measured with RT-PCR methods.Apoptosis and expressions of Bcl-2 and Bax were respectively determined by flow cytometry (FCM) and immunohistochemistry (IHC).The pathological changes of lung tissue were observed under light and electron microscope.RESULTS: Compared with that in control group,the expression of iNOS mRNA was significantly increased at 3,6,9 and 12 h after administration of LPS (P<0.05).The eNOS mRNA was significantly decreased at 3,6,9 and 12 h after administration of LPS (P<0.05).The nNOS mRNA had no significant change during the 12 h in LPS group.Degree of ALI was gradually worsened after administration of LPS.Apoptosis of pulmonary cells was significantly increased,and reached the top level at 9 h after administration of LPS (P<0.01).The expression of Bcl-2 was markedly decreased and the expression of Bax was significantly enhanced in alveolar and airway epithelial cells in LPS treated group.CONCLUSION: The expressions of iNOS mRNA,eNOS mRNA and nNOS mRNA are not identical in LPS-induced acute lung injury.NOS regulates the apoptosis of pulmonary cells through affecting the balance of Bcl-2 and Bax.     

Protective effect of recombinant human serum albumin-thioredoxin fusion protein on mice with acute lung injury induced by influenza virus

AIM To investigate the protective effect of recombinant human serum albumin (HSA)-thioredox?in (Trx) fusion protein (HSA-Trx) on mice with acute lung injury (ALI) induced by influenza virus infection. METH?ODS: The recombinant HAS-Trx fusion protein was generated by Pichia pastoris expression system. ICR mice were used to establish the animal model of ALI induced by PR8 (H1N1) influenza virus, and the experimental mice were divided into healthy control group, ALI group, ALI+Trx group and ALI+HSA-Trx group, with 10 mice in each group. The bronchoalveolar lavage fluid (BALF) in each group was collected, the total number of cells and the number of alveolar neutrophils were determined, the protein concentration was measured by Coomassie brilliant blue solution method, and the interferon-γ (IFN-γ) content in BALF was detected by ELISA. The lung tissues were collected for hematoxylin and eosin staining. The inducible nitric oxide synthase (iNOS), 8-hydroxydeoxyguanosine (8-OHdG) and 3-nitrotyrosine (NO₂-Tyr) in lung tissues were detected by immunofluorescence method. Peroxide concentration in plasma was evaluated using a CR2000RC analyzer. RESULTS HSA-Trx treatment significantly reduced the total number of cells, neutrophils and total protein in BALF of ALI mice (P<0.05), and decreased the levels of 8-OHdG, NO₂-Tyr in lung tissue and peroxide in plasma (P<0.05). However, it has no significant inhibitory effect on iNOS and IFN-γ expression (P>0.05). CONCLUSION HSA-Trx inhibits inflammatory response and excessive production of nitric oxide in the lung, thus protecting influ?enza virus-induced ALI mice.     

Protective effects of hypercapnia on acute lung injury and it's mechanisms

AIM: To investigate whether hypercapnia is protective against acute lung injury (ALI) in a rabbit model, and study it's potential mechanisms. METHODS: Twenty-two healthy New Zealand white rabbits were involved in this study, and randomly allocated to control group (group C), normocapnic group (group N) and hypercapnic group (group H). Oleic acid (0.1 mL/kg) was injected intravenously to establish ALI model. Lung mechanics, hemodynamics, blood-gas analysis, the content of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in lung tissue were measured. Apoptosis was analyzed after 3h mechanical ventilation. RESULTS: (1) Peak airway pressure in group H was significantly lower than that in group N (P<0.05) and the dynamic lung compliance was significantly higher than that in group N (P<0.05). (2) PaO₂ in group H was significantly higher than that in group N(P<0.05). (3) The content of MDA was significantly lower but the activity of SOD was significantly higher in group H than that in group N (P<0.05). (4) Apoptosis index in group H was significantly lower than that in group N (P<0.01). (5) Histologic damage was significantly severer in group N than group H. (6) PaCO₂ was correlated with pH, PaO₂, dynamic lung compliance, peak airway pressure and pulmonary permeability index (r=－0.928, P<0.01; r=0.511, 0.526, -0.506, -0.556, P<0.05, respectively). CONCLUSION: Hypercapnia protects lung from oleic acid-induced injury in rabbits. The mechanisms of protection might be associated with improvement of oxidation/anti-oxidation imbalance and inhibition of apoptosis.     

Expression and significance of angiopoietin-2 and Tie-2 receptors in a rat model of acute lung injury

AIM: To explore the expressions and significance of angiopoietin-2 (Ang-2) and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 (Tie-2) receptors in a rat model of acute lung injury (ALI). METHODS: Wistar rats (n=42) were divided into control group (n=12) and cecal ligation and puncture (CLP) group (n=30). Control group underwent sham operation, and CLP group underwent cecal ligation and puncture to make the model of ALI. 12 h after sham operation or CLP, 6 rats in each group were killed, and arterial blood gas analysis and lung coefficient were tested. The expressions of Ang-2 and Tie-2 receptors in lung tissue were observed by immunohistochemical method. Blood samples of the rest rats were collected from vena caudalis, and Ang-2 levels were measured by enzyme linked immunosorbent assay (ELISA). The mortality rate in each group within 36 h was compared. The lung architecture was observed under microscope. RESULTS: The lung architecture in control group was clear and intact. Alveolar septum was thicker, blood capillary was congested, and neutrophils and macrophages were infiltrated in the lung tissue in CLP group. Tie-2 receptors were expressed in bronchial epithelial cells, smooth muscle cells and endothelial cells in control group. Besides the similar expression as control group, high expression of Tie-2 on neutrophils and macrophages in CLP group was observed. In the adhesion location of Tie-2 receptors positive inflammatory cells, there was stronger staining in endothelial cells. Ang-2 was expressed in smooth muscle cells, bronchial epithelial cells and endothelial cells in control group. The Ang-2 level in CLP group were higher than that in control group ［(8.14±1.74) μg/L vs (4.63±0.49) μg/L, P<0.01］, and the Ang-2 level of dead rats was higher than that of survival rats within 36 h in CLP group ［(8.95±1.61)μg/L vs (6.80±0.96)μg/L, P<0.01］. Oxygen partial pressure in control group was lower (P<0.01) and lung coefficient was higher (P<0.01) than that in CLP group. CONCLUSION: Ang-2 and Tie-2 receptors may participate in the pathophysiology of ALI, and Ang-2 level is correlated with mortality.     

Effect of the combination of positive end expiratory pressure and nitric oxide inhalation on oleic acid-induced acute lung injury in canine

AIM:To observe the effects of the combination of positive end expiratory pressure (PEEP) and 80×10^-6 nitric oxide (NO) inhalation on oleic acid induced acute lung injury (ALI) in canine.METHEDS:30 dogs were divided into 6 groups. Oleic acid was injected through Swan-Ganz catheter to induced ALI. Pulmonary and systemic hemodynamics,blood gas were measured in dogs before and after injection of oleic acid and the period of inhaled NO for 1-6 h. The methemoglobin(MHb) concentrations were measured. Histology and ultrastructure of the lung tissue were observed. RESULTS:(1) The combination of PEEP and 80×10^-6 NO inhalation rapidly reduced mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR), increased PaO₂/FiO₂, reduced A-aDO₂ without inducing significant change on systemic hemodynamics. Arterial blood levels of MHb did not change significantly. (2)The combination group was showed the lightest ALI change by HE stain and electron microscopy. CONCLUSION:The combination of PEEP and inhalation of 80×10^-6 NO significantly and rapidly increased PaO₂/FiO₂ without producing lung injury induced by high FiO₂ and high PEEP.     

Effects of partial liquid ventilation on acute lung injury in piglets

AIM: To observe the effect of partial liquid ventilation with perfluorocarbon on gas exchange, hemodynamics and lung histological change in the piglets with surfactant depletion-induced acute lung injury. METHODS: 12 piglets were treated by lung lavage to a partial pressure of oxygen in arterial blood (PaO₂) below 100 mmHg for one hour and randomly divided into gas ventilation group (control group) and partial liquid ventilation (PLV) group, in PLV group, piglets received PFC (FC3280) intratracheally at doses of 15 mL/kg. The parameters of gas exchange and hemodynamics were measured before lung lavage, after lung lavage when the acute lung injury (ALI) was established, and 1 hour, 2 hours after ALI. Animals underwent euthanasia at the end of the study, lung histologic analysis followed. RESULTS: Surfactant depletion by lung lavage induced a stable acute lung injury.Gas exchange increased markedly in the animals that underwent PLV, less hemodynamic damage was observed in PLV group compared with the animals in GV group. Lung histologic analysis demonstrated a less lung damage, including atelectasis, neutrophil excudation, intra-alveolar hemorrhage and interstitial edema in PLV group compared with control group. CONCLUSION: In piglets with surfactant depletion-induced acute lung injury, partial liquid ventilation with perfluorocarbon can improve the gas exchange with less adverse hemodynamic effect and less lung injury compared with conventional gas ventilation.     

Effect of DADLE on lung injury in rats with acute global cerebral ischemia-reperfusion

AIM：To observe the effects of δ opioid receptor agonist DADLE on acute lung injury (ALI) induced by acute global cerebral ischemia-reperfusion in rats. METHODS：SD rats (n=30) were randomly divided into sham group, model (I/R) group and DADLE treatment group. Global cerebral ischemia-reperfusion model was established by a modified 2-vessel occlusion plus hypotension. DADLE (5 mg/kg) treatment was performed via the left jugular injection before reperfusion. After 120-min reperfusion, the pathological changes of the lung tissues were observed under light microscope and electronic microscope. The activity of superoxide dismutase (SOD) and malondialdehyde (MDA) level were detected. The partial pressure of arterial oxygen (PaO2) was also measured. RESULTS：In I/R group, widened alveolar septum, capillary dilatation and congestion, endovascular and perivascular cells in the lung with neutrophil infiltration, and significantly reduced type II epithelial cell surface microvilli, alveolar lumen cavity and trachea with serous exudate were observed. SOD activity decreased, but the MDA level increased. Compared with I/R group, the SOD activity increased and MDA level decreased in DADLE treatment group, with significantly reduced lung congestion, the degree of lung injury, and the infiltration of neutrophils. Compared with I/R group, the PaO2 and oxygenation index in DADLE treatment group were increased. CONCLUSION：Various degrees of pulmonary injury were observed in acute global cerebral ischemia reperfusion model. DADLE might have a protective effect on lung tissues of ALI in rats.