1.Advances in the study of the relationship between autophagy and sepsis-induced lung injury.
Xingtong WANG ; Hengyu LI ; Zhaofan XIA
Chinese Journal of Burns 2014;30(4):325-328
Sepsis is one of the most common pathogenetic causes of acute lung injury (ALI), and at present there is still a lack of effective targeted techniques and methods for its prevention and treatment. Autophagy is a homeostatic mecha- nism common to all eukaryotic cells, including adaption to environment, defense against invasion of pathogens, and maintenance of cellular homeostasis. Autophagy is also involved in a variety of lung-related diseases. In septic lung injury, autophagy not only serves to dissipate dysfunctional organelles, but also inhibits the release of inflammatory cytokines. This review aims at eliciting the role of autophagy in sepsis-induced ALI and further exploring the potential targets of autophagy in inhibiting inflammation, in an effort to provide a new perspective for clinical treatment of sepsis-induced ALI.
Acute Lung Injury
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etiology
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metabolism
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Autophagy
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Cytokines
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metabolism
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Inflammation
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metabolism
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Lung
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metabolism
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Lung Injury
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Sepsis
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complications
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metabolism
2.Expression NOS in acute lung injury following limb ischemia/reperfusion and its significance in rats.
Yi-Bing ZHANG ; Lian-Yuan ZHANG ; Xiu-Li MEN ; Shu-Yun DONG ; Quan-Hui YANG ; Rui-Li YAO
Chinese Journal of Applied Physiology 2006;22(4):484-487
AIMTo investigate the expression and role of inducible NOS (iNOS) and endothelial NOS (eNOS) in acute lung injury following limb ischemia/reperfusion (4h/4h).
METHODSWistar rats were randomized into four groups: control group, ischemia/reperfusion (I/R) group, L-Arginine (L-Arg) pretreatment group, Aminoguanidine (AG) pretreatment group. The lung tissue of each group was subjected to assay of content of MDA, MPO, W/D and NO2-/NO3-. The expression of iNOS and eNOS was examined with immunohistological staining. The pulmonary morphologic changes were observed under microscope respectively.
RESULTSThe acute lung injury existed after limb ischemia/reperfusion. The eNOS downregulation and iNOS upregulation among I/R, L-Arg and AG groups were observed contrasted to the control group. There was no expressional and statistical difference of iNOS between I/R group and L-Arg group. The expression of eNOS was similar between IR and AG but iNOS expression was downregulated in AG. The parameters of MDA, MPO, W/D and NO2-/NO3- in pulmonary tissue were significantly increased in I/R groups compared with those of the control group. The parameters of L-Arg and AG pretreatment groups in comparison with those of the I/R group showed significantly difference. Based on the results of pulmonary pathology, the congestion and infiltration of inflammatory cells existed obviously in IR group. L-Arg played definite role in militating lung injury and AG might make lung injury aggravated.
CONCLUSIONThe NO definite production from iNOS is possible to play a competitivly protective role in acute lung injury following limb ischemia/reperfusion and antagonist of iNOS may aggravate the lung injury.
Acute Lung Injury ; etiology ; metabolism ; Animals ; Extremities ; blood supply ; Male ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism
3.Observation on the protective effect of hyperoxia solution on the acute lung injury caused by phosgene poisoning..
Ling WANG ; Li-xian XU ; Chun-xu HAI ; Shi-rong TANG ; Xu-ju QIN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2005;23(1):20-23
OBJECTIVETo study the protective effect of hyperoxia solution on acute lung injury caused by phosgene poisoning by observing the changes of PaO2 and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity in serum and Glutathione (GSH/GSSG) contents in lung tissues.
METHODSThe rabbits were divided into normal control group, hyperoxia solution (H0) and balance salt (BS) groups. Group HO and Group BS inhaled phosgene and the former was given intravenously hyperoxia solution (which was replaced by balance salt solution in Group BS). The content of MDA and the activity of SOD in serum were observed at different time points, the amount of GSH and GSSG in lung tissue were also measured.
RESULTS(1) The serum MDA contents increased and PaO2, SOD activity decreased significantly in Group HO and Group BS along with time increasing as compared with control group. The contents of GSH in lung tissue decreased in two groups compared with that in control group, however the contents of GSSG ascended instead. (2) At 3 and 8 h of the experiment, PaO2 of Group HO [(9.91 +/- 0.49), (9.15 +/- 0.46) mm Hg respectively] were significantly higher than those of Group BS [(9.03 +/- 0.76), (8.11 +/- 0.57) mm Hg respectively] (P < 0.01). The contents of MDA of Group HO (3.66 +/- 0.35), (5.31 +/- 0.15) micromol/L respectively] were lower than those of Group BS [(4.32 +/- 0.26), (7.4 +/- 0.33) micromol/L respectively] (P < 0.01). SOD activity in Group HO [(237.37 +/- 29.96), (208.10 +/- 18.80) NU/ml respectively] were higher than those of Group BS [(195.02 +/- 21.44), (144.87 +/- 21.26) NU/ml respectively] (P < 0.05 or P < 0.01). The content of GSSG lung tissue in Group HO (423.67 +/- 38.21) micromol/L were lower than those of Group BS (523.85 +/- 43.14) mol/L (P < 0.01). There were no significant differences in the content of GSH in lung tissues between Group HO and group BS.
CONCLUSIONHyperoxia solution can reduce acute lung injury of rabbits following phosgene poisoning.
Acute Lung Injury ; etiology ; metabolism ; pathology ; Animals ; Glutathione Peroxidase ; metabolism ; Hyperoxia ; Lung ; drug effects ; metabolism ; pathology ; Malondialdehyde ; analysis ; Oxygen ; administration & dosage ; pharmacology ; Phosgene ; poisoning ; Rabbits ; Superoxide Dismutase ; metabolism
4.Effects of hydrocortisone on oxygen free radicals released by polymorphonuclear neutrophils in lipopolysaccharide-induced acute lung injury in mice.
Li ZHANG ; Kun-ling SHEN ; Tao ZHOU ; Yue-qiang XUE ; Peng YANG
Chinese Journal of Pediatrics 2004;42(9):659-662
BACKGROUNDCorticosteroid treatment of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) has been one of the most controversial clinical issues in critical care. Although the administration of high-dose corticosteroids does not benefit patients with early septic shock and ARDS, recent clinical trials have indicated that treatment with relatively low-dose corticosteroids (2 to 3 mg/kg/day of methylprednisolone or equivalent) may improve outcome when used for late ARDS or persistent septic shock. The underlying mechanism was not fully clarified. Whether the administration of corticosteroids can arrest neutrophil-driven organ injury once started remains to be elucidated.
OBJECTIVETo observe the effects of hydrocortisone (HC, 6 mg/kg) on oxygen free radicals (OFR) released by PMN and pulmonary pathological changes in rat ALI model induced by lipopolysaccharide (LPS), to investigate the possible mechanism through which corticosteroids exert protective effect on ALI.
METHODSA rat model of ALI was induced by peritoneal injection of 2 x 10(12) Escherichia coli/kg. Fifty-six rats were randomly divided into three groups: normal control group, LPS group and HC group (6 mg/kg). Samples were collected 2 h, 4 h and 6 h after giving LPS to LPS and HC group (6 h after giving normal saline in normal control group) to measure the level of OFR released by PMN using chemiluminescence method based on lumino, and to compae of pulmonary pathological changes among the three groups.
RESULTSPathological examination with light microscope in LPS group showed thickened pulmonary interstitia, inflammatory cell infiltration, edema and hemorrhage, which were in accordance with the features of ALI. There were significant differences in the release of OFR by PMN among the three groups (P < 0.01). The level of OFR released by PMN in LPS group was significantly higher than that of the control group, and continued to increase during the observation period (2 - 6 h after LPS). The release of OFR by PMN in HC group was significantly suppressed as compared with LPS group, which was peaked at 4 h after LPS injection (to 98.2%); there were also significant differences in the grades of ALI pathologic changes among the three groups (P < 0.01). The grades of ALI pathologic changes in LPS group were significantly increased when compared with the normal control group (P < 0.05) while significantly decreased in HC group as compared with LPS group (P < 0.05).
CONCLUSIONIt was demonstrated in the LPS induced ALI model that OFR might play an important role in onset of ALI. Intervening with HC (6 mg/kg) treatment could ameliorate the lung injury and exert significant and sustained suppression on the release of OFR by PMN, showing that HC has a protective effect on LPS induced ALI and its theraputic effect occurs possibly through suppression on the release of OFR by PMN.
Acute Lung Injury ; etiology ; immunology ; Animals ; Disease Models, Animal ; Free Radicals ; metabolism ; Glucocorticoids ; pharmacology ; Hydrocortisone ; pharmacology ; Lipopolysaccharides ; adverse effects ; Lung ; immunology ; pathology ; Mice ; Neutrophils ; drug effects ; metabolism
5.The relationship between HIF-1α expression and the early lung fibrosis in rats with acute paraquat poisoning.
Rui-lan WANG ; Xue TANG ; Xin WU ; Rong XU ; Kang-long YU ; Kan XU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2012;30(4):273-277
OBJECTIVETo explore the role of hypoxia-inducible factor 1alpha (HIF-1α) in early lung fibrosis of rats with acute paraquat (PQ) poisoning.
METHODSForty eight healthy SD rats were randomly divided into control group (6 rats) and paraquat poisoning group (42 rats). Control group was exposed to 1 ml normal solution by gastric gavage. The paraquat group was exposed to 1 ml paraquat solution (50 mg/kg) by gastric gavage for 2, 6, 12, 48, 72 and 120 h, respectively. The arterial blood gas analysis (PaO(2)) was detected. The pathological examinations of lung tissues were performed by HE and Mason staining. HIF-1α in lung tissues were measured by immunofluorescence. Western blot assay was used to detect the expression levels of HIF-1α protein in lung tissues.
RESULTSPaO2 of rats exposed to paraquat for 72 h was (62.33 ± 0.22) mm Hg, which was significantly lower than that (96.00 ± 5.20) of control group (P < 0.05). Pathological examination by HE staining indicated that the acute diffuse lesion appeared in the alveolar capillary endothelium, epithelia and interstitial tissues, and there was the inflammatory cell infiltration in the alveolar of rats exposed to paraquat at 2 h after exposure. At 12 h after exposure, the interstitial edema in lung tissues of rats decreased and the alveolar space became narrow. At 120 h after exposure, there were the alveolar structure derangement, abundant cicatrix, more fibroblasts and peripheral inflammation absorption. Pathological examination by Masson staining showed that there was obvious collagen deposition in the alveolar epithelia at 2h after exposure, the increased collagen fibrosis at 24 and 48 h after exposure and the obvious damage of alveolar tissues or much more fibrous connective tissue deposition at 120 h after exposure. The results of western blot and immunofluorescence assays exhibited that the expression levels of HIF-1α in lung tissues at 2, 24 and 48 h after exposure significantly increased, as compared with control group (P < 0.05), but there were no significant differences of HIF-1α expression among sub-groups at different time points after exposure.
CONCLUSIONThe results of present study shown that there were the pulmonary fibrosis and increased expression of HIF-1α in acute PQ poisoning rats at the early stage, and HIF-1α may be associated with pulmonary fibrosis.
Acute Lung Injury ; chemically induced ; complications ; metabolism ; Animals ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Paraquat ; poisoning ; Pulmonary Fibrosis ; etiology ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley
6.Protective effects of ulinastatin on phosgene-induced acute lung injury and relation to matrix metalloproteinase-9.
Wen-bin HUANG ; Jie SHEN ; Lin ZHANG ; Dai-kun HE ; Tie XU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2010;28(7):498-504
OBJECTIVETo observe the protective mechanism of ulinastatin on mice with acute lung injury induced by exposure to phosgene and its relationship to the expressions of matrix metalloproteinase-9 (MMP-9) in the lung tissues.
METHODSSixty-four healthy male SD rats were randomly divided into two groups: the experimental group and the control group. 32 rats in the experiment group were randomly subdivided into four groups: rats with phosgene exposure group, rats with phosgene exposure after saline injected group, rats with phosgene exposure after dexamethasone injected group. 32 rats in the control group were randomly subdivided into four groups: rats with air exposure group, pretreated with ulinastatin before air exposure group, pretreated with saline before air exposure group, pretreated with dexamethasone before air exposure group, 8 animals in each group. After pretreated with the same dose of ulinastatin, saline, dexamethasone respectively, 32 rats in the control groups were exposed to the air on the same condition respectively for 5 min. While after pretreated with the same dose of ulinastatin, saline, dexamethasone respectively, 32 rats in the experiment groups were exposed to the phosgene which the concentration was 8.33 mg/L and with 100% purity for 5 min. The lung wet/dry (W/D) weight ratio was calculated, and total protein content and BALF leukocyte count were detected. The immunohistochemistry was used to detect lung tissue protein expression MMP-9 while enzyme-linked immunosorbent method was employed to detect MMP-9 in serum levels and enzyme original gelatinases spectrum method to detect BALF MMP-9 enzyme original content.
RESULTSCompared with A1, A2, A3, A4 group, the lung W/D, BALF of protein content and WBC count in B1 and B2 group rats were significantly increased, and the difference was statistically significant (P < 0.01). There was statistically significant difference in lung W/D, BALF of protein content and white blood cell count between B1,B2 group and the B3 and B4 rats (P < 0.01). Histological experimental results showed marked hyperemia of alveolar walls, thickening in the lungs, alveolar walls and stroma cells infiltrating and more visible alveolar structure damage in B1 and B2 rats while the alveolar structure, the alveolar walls were clear and slightly thickened with inflammatory cells in B3 and B4 rats. Immunohistochemical result showed that the individual rats, lung and bronchus organization MMP-9 protein were weakly positive, B1 and B2 group MMP-9 protein expression was strongly positive,B3 group and the group MMP B4 lung tissue protein expression-9 weakens, restored to the normal lung tissue of weakly positive expression level. ELISA and gelatinases spectrum testing showed B1 and B2 rats, serum MMP-9 enzyme activity and content increased compared with A1, A2, A3, A4 group, the differences were statistically significant (P < 0.01), and B1, B2 group compared with the B3 and serum B4 group MMP-9 enzyme activity and the differences were obviously decreased, with statistically significant difference (P < 0.01).
CONCLUSIONSUlinastatin has protective effect on phosgene-induced ALL Ulinastatin can inhibit the up-regulation of expression of MMP-9.
Acute Lung Injury ; drug therapy ; etiology ; metabolism ; Animals ; Glycoproteins ; therapeutic use ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Phosgene ; toxicity ; Rats ; Rats, Sprague-Dawley
7.Protective mechanisms of sevoflurane against one-lung ventilation-induced acute lung injury: role of cyclooxygenase-2 and 5-lipoxygenase pathways.
Rui LIU ; Jing LUO ; Jiang LI ; Qingjie MA ; Jingzhe SUN ; Yanhua LI ; Dianhua WANG
Journal of Southern Medical University 2013;33(5):625-630
OBJECTIVETo explore the protective mechanisms of sevoflurane against acute lung injury (ALI) induced by one-lung ventilation (OLV) in view of cyclooxygenase-2 (COX2) and 5-lipoxygenase (5-LOX) pathways.
METHODEighteen healthy Japanese white rabbits were randomized into sham-operated group (S group), OLV group (O group) and OLV + sevoflurane group (OS group). COX2 and 5-LOX protein and mRNA expressions in the lungs were detected by Western blotting and real-time PCR, respectively. Prostaglandin I2 (PGI2), thromboxane A2 (TXA2) and leukotrienes B2 (LTB2) in the lung tissues were quantified with ELISA. Histological scores and lung wet/dry weight (W/D) ratios were determined for lung injury assessment.
RESULTSCOX2 and 5-LOX protein and mRNA expressions and the contents of LTB2, TXA2 and PGI2 in the lungs, lung W/D ratio and histological scores were significantly higher while PGI2/TXA2 ratio was significantly lower in O group and OS group than in S group (P<0.05). Compared with those in O group, COX2 and 5-LOX expressions, pulmonary contents of LTB2, TXA2 and PGI2, and lung W/D ratio all decreased significantly but PGI2/TXA2 ratio was significantly elevated in OS group (P<0.05).
CONCLUSIONOLV may activate COX2 and 5-LOX pathways to result in increased production of arachidonic acid metabolites. Sevoflurane protects against OLV-induced ALI probably by reducing AA metabolites and regulating PGI2/TXA2 ratio through inhibitions of COX2 and 5-LOX pathways.
Acute Lung Injury ; etiology ; metabolism ; Animals ; Arachidonate 5-Lipoxygenase ; metabolism ; Cyclooxygenase 2 ; metabolism ; Lung ; drug effects ; metabolism ; Methyl Ethers ; adverse effects ; One-Lung Ventilation ; adverse effects ; RNA, Messenger ; genetics ; Rabbits
8.Role of epithelial sodium channel alpha subunit in terbutaline-induced transient enhancement of pulmonary edema clearance in adult rats with acute lung injury.
Dong-xiang HUANG ; Tao-ping LI ; Lin HE
Journal of Southern Medical University 2009;29(5):868-871
OBJECTIVETo explore the association of epithelial sodium channel alpha subunit (alphaENaC) with terbutaline-induced transient enhancement of pulmonary edema clearance in adult rats with acute lung injury (ALI).
METHODSThe effect of 1-h intratracheal terbutaline treatment on pulmonary edema clearance in adult rats with experimental ALI was observed by blood gas analysis, lung tissue HE staining, and extravascular lung water (EVLW) content measurement. The mRNA and protein expressions of alphaENaC in the lung tissues were detected by fluorescence quantitative real-time RT-PCR and Western blotting, respectively.
RESULTTerbutaline treatment of the rats with ALI resulted in significant differences in PaO2, oxygenation index, and EVLW from those in ALI group without treatment. No significant differences in pulmonary alphaENaC mRNA and protein expressions were noted between the normal control, ALI, and terbutaline-treated ALI groups.
CONCLUSIONSIntratracheal terbutaline administration for 1 h can significantly promote pulmonary edema clearance in adult rats with ALI, and this effect is not mediated by alphaENaC gene expression.
Acute Lung Injury ; chemically induced ; complications ; drug therapy ; genetics ; metabolism ; Animals ; Epithelial Sodium Channels ; genetics ; metabolism ; Female ; Male ; Oleic Acid ; Pulmonary Edema ; drug therapy ; etiology ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Terbutaline ; therapeutic use
9.Acute lung injury induced by H9N2 virus in mice.
Yan LI ; Yunfeng SHAN ; Ying CHI ; Tian WEN ; Xiaodong HAN
Chinese Medical Journal 2014;127(20):3576-3580
BACKGROUNDH9N2 avian influenza viruses (AIVs) have repeatedly caused infections in mammals even humans in many countries. The purpose of our study was to evaluate the acute lung injury (ALI) caused by H9N2 viral infection in mice.
METHODSSix- to eight- week-old female SPF C57BL/6 mice were infected intranasally with 1 × 10(4) MID50 of A/HONG KONG/2108/2003 [H9N2 (HK)] virus. Clinical signs, pathological changes, virus titration in tissues of mice, arterial blood gas, and cytokines in bronchoalveolar lavage fluid (BALF) and serum were observed at different time points after AIV infection.
RESULTSH9N2-AIV-infected mice exhibited severe respiratory syndrome, with a mortality rate of 50%. Lung histopathological changes in infected mice included diffuse pneumonia, alveolar damage, inflammatory cellular infiltration, interstitial and alveolar edema, and hemorrhage. In addition, H9N2 viral infection resulted in severe progressive hypoxemia, lymphopenia, and a significant increase in interleukin 1, interleukin 6, tumor necrosis factor, and interferon in BALF and serum.
CONCLUSIONSThe results suggest that H9N2 viral infection induces a typical ALI in mice that resembles the common features of ALI. Our data may facilitate the future studies of potential avian H9N2 disease in humans.
Acute Lung Injury ; blood ; etiology ; virology ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Female ; Influenza A Virus, H9N2 Subtype ; pathogenicity ; Interleukin-1 ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Mice ; Mice, Inbred C57BL ; Respiratory System ; virology ; Tumor Necrosis Factor-alpha ; blood ; metabolism
10.Protective role of MMP-9 inhibitor batimastat in acute lung injury after cardiopulmonary bypass.
Sheng-lin GE ; Wen-hui GONG ; Cheng-xin ZHANG ; Lei ZHANG ; Pei-hua HAN ; Sheng-quan ZHANG ; Jun-bo FENG ; De-cun ZHOU
Chinese Journal of Surgery 2010;48(1):57-61
OBJECTIVETo investigate the protective effect of exogenous inhibitor of matrix metalloproteinases-9 (MMP-9), batimastat, in the lung injury induced by cardiopulmonary bypass (CPB) in dogs.
METHODSThirty healthy mongrel puppies were randomly divided into 3 groups: control group, low-dose group [batimastat 10 mg/(kg.d) for 3 days before operation] and high-dose group [batimastat 30 mg/(kg.d) for 3 days before operation]. The off-pump puppies' model of acute lung injury was established, and hemodynamic and respiratory parameters were monitored. The preoperative and postoperative alveolar-arterial oxygen difference (A-aDO(2)) and respiratory index (RI) were calculated. From the beginning of surgery, blood samples were taken at the time 0, 60, 120, and 270 min. Plasma concentrations of MMP-9 were measured by ELISA, and blood MMP-9 mRNA expressions were determined by RT-PCR. The myeloperoxidase (MPO) activity of centrifugal bronchoalveolar lavage fluid were measured by Colorimetry. And MMP-9 activity was determined by Gelatin zymography. Light and electronic microscope were used to observe the morphological changes of lung tissue. A small piece of left lung tissue was taken, weighed and baked to calculate the wet weight (W/D) index.
RESULTSAfter cardiopulmonary bypass, the concentrations of MMP-9 and mRNA expressions of the control group were increased significantly, and lung injury was apparent. At 270 min, the MMP-9 plasma concentration of high-dose group (17.36 +/- 1.18) microg/L was significant reducing than control group (30.47 +/- 2.22) microg/L (P < 0.05). After operation, A-aDO(2) and RI of high-dose group were significantly improved than control group (P < 0.05). The W/D index of the high-dose group (2.8 +/- 0.48) was significantly lower than that of control group (4.7 +/- 0.6) (P < 0.05). And the pathological changes of lung tissue were significantly improved in the high-dose group. However, there was no significant difference in the MMP-9 mRNA expression in three groups.
CONCLUSIONSBatimastat plays a role in the protection of the lung injury of CBP by reducing the concentration and activity of MMP-9, the degradation of the cell membrane and pulmonary neutrophil infiltration and reduction of pulmonary edema.
Acute Lung Injury ; etiology ; prevention & control ; Animals ; Cardiopulmonary Bypass ; Disease Models, Animal ; Dogs ; Lung ; pathology ; Matrix Metalloproteinase 9 ; metabolism ; Matrix Metalloproteinase Inhibitors ; Phenylalanine ; analogs & derivatives ; pharmacology ; Postoperative Complications ; prevention & control ; Thiophenes ; pharmacology