OBJECTIVETo study the expression of SUMO-modified CCAAT enhancer binding protein α (C/EBPα) in preterm rat model of bronchopulmonary dysplasisa (BPD) induced by hyperoxia exposure and its role.

METHODSEighteen preterm rats were randomly divided into an air group and a hyperoxia group (n=9 each). The model of BPD was prepared in preterm rats exposed to hyperoxia. The rats from the two groups were sacrificed on postnatal days 4, 7 and 14 respectively (3 rats at each time) and lung tissues were harvested. Periodic acid-Schiff (PAS) staining was used to observe the differentiation of rat lung tissues. Ki67 expression was detected by immunohistochemistry. Western blot was used to measure the protein expression of small ubiquitin-related modifier-1(SUMO1) and C/EBPα. A co-immunoprecipitation assay was performed to measure the protein expression of SUMO-modified C/EBPα.

RESULTSCompared with the air group, the hyperoxia group showed a decreased glycogen content in the lung tissue on postnatal day 4, and an increased content on postnatal days 7 and 14. Over the time of hyperoxia exposure, the hyperoxia group showed an increased expression of Ki67 in the lung tissue compared with the air group at all time points. Compared with the air group, the protein expression of C/EBPα increased on postnatal day 4 and decreased on postnatal days 7 and 14 in the hyperoxia group (P<0.05). The hyperoxia group had significantly upregulated expression of SUMO1 and SUMO-modified C/EBPα compared with the air group at all time points (P<0.05). In the hyperoxia group, the protein expression of SUMO-modified C/EBPα was positively correlated with the glycogen content (r=0.529, P<0.05) and the expression of Ki67 (r=0.671, P<0.05).

CONCLUSIONSHyperoxia may induce over-proliferation and differentiation disorders of alveolar epithelial cells in preterm rat model of BPD, possibly through an increased expression of SUMO-modified C/EBP&alpha.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; etiology ; metabolism ; pathology ; CCAAT-Enhancer-Binding Protein-alpha ; metabolism ; Cell Proliferation ; Disease Models, Animal ; Hyperoxia ; complications ; pathology ; Ki-67 Antigen ; analysis ; Pulmonary Alveoli ; pathology ; Rats ; Rats, Sprague-Dawley ; Sumoylation

We observed a rare case of invasive mucinous adenocarcinoma (IMA) with a lepidic-predominant pattern accompanied by pulmonary tuberculosis. An 85-year-old man with repeated cough and sputum was admitted to Xinhua Hospital. T-SPOT test result was 212 pg/ml (reference value of negative is < 14 pg/ml), Mycobacterium tuberculosis culture was positive, and tuberculin skin test (PPD) was negative (skin induration < 5 mm). The patient was treated with several courses of antibiotics and anti-tuberculosis treatments. Repeated chest CT scans showed disease progression. Bronchoscopy yielded negative results. PET-CT scans showed negative results. A percutaneous lung biopsy revealed mucin-secreting cells lining the alveolar walls. IMA with a lepidic-predominant pattern was diagnosed after invasiveness was found after experimental treatments. Simultaneous occurrence of pulmonary tuberculosis and lung cancer are common; however, the present case of IMA having a lepidic-predominant pattern and coexisting with active tuberculosis has not been reported yet.
Adenocarcinoma, Mucinous ; diagnosis ; pathology ; Aged, 80 and over ; Antibiotics, Antitubercular ; therapeutic use ; Disease Progression ; Humans ; Lung Neoplasms ; diagnosis ; pathology ; Male ; Mycobacterium tuberculosis ; isolation & purification ; Positron Emission Tomography Computed Tomography ; Pulmonary Alveoli ; pathology ; Tuberculosis, Pulmonary ; diagnosis ; drug therapy

OBJECTIVETo study the association between endoplasmic reticulum stress (ERS) pathway mediated by inositol-requiring kinase 1 (IRE1) and the apoptosis of type II alveolar epithelial cells (AECIIs) exposed to hyperoxia.

METHODSThe primarily cultured AECIIs from preterm rats were devided into an air group and a hyperoxia group. The model of hyperoxia-induced cell injury was established. The cells were harvested at 24, 48, and 72 hours after hyperoxia exposure. An inverted phase-contrast microscope was used to observe morphological changes of the cells. Annexin V/PI double staining flow cytometry was performed to measure cell apoptosis. RT-PCR and Western blot were used to measure the mRNA and protein expression of glucose-regulated protein 78 (GRP78), IRE1, X-box binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP). An immunofluorescence assay was performed to measure the expression of CHOP.

RESULTSOver the time of hyperoxia exposure, the hyperoxia group showed irregular spreading and vacuolization of AECIIs. Compared with the air group, the hyperoxia group showed a significantly increased apoptosis rate of AECIIs and significantly increased mRNA and protein expression of GRP78, IRE1, XBP1, and CHOP compared at all time points (P<0.05). The hyperoxia group had significantly greater fluorescence intensity of CHOP than the air group at all time points. In the hyperoxia group, the protein expression of CHOP was positively correlated with the apoptosis rate of AECIIs and the protein expression of IRE1 and XBP1 (r=0.97, 0.85, and 0.88 respectively; P<0.05).

CONCLUSIONSHyperoxia induces apoptosis of AECIIs possibly through activating the IRE1-XBP1-CHOP pathway.

Animals ; Apoptosis ; Cells, Cultured ; Endoplasmic Reticulum Stress ; physiology ; Endoribonucleases ; physiology ; Epithelial Cells ; physiology ; Female ; Hyperoxia ; metabolism ; pathology ; Multienzyme Complexes ; physiology ; Protein-Serine-Threonine Kinases ; physiology ; Pulmonary Alveoli ; pathology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor CHOP ; physiology ; X-Box Binding Protein 1 ; physiology

OBJECTIVETo explore the expression of CASZ1 and its relationship with the pulmonary microvascular development in lung tissue of newborn rats exposed to hyperoxia which induced bronchopulmonary dysplasia (BPD).

METHODForty-eight newborn Sprague Dawley(SD) rats (male and female unlimited) were randomly divided into two groups: experimental group and control group according to random digits table with 24 in each.The rats in experimental group were exposed to high oxygen volume fraction of 800 ml/L and the rats in control group were exposed to normal air. Eight rats were randomly selected from each group on day 3 and 7 after oxygen exposure.The sections of lung were stained with HE method in order to assess lung histological changes, the alveolar development was evaluated by the number of radial alveolar count (RAC) and septal wall thickness. CD31 was detected by immunohistochemistry (IHC) method and the capillary density was calculated. The location, distribution and expression of CASZ1 in the lung tissue were detected by the immunohistochemistry, Western blotting, and quantitative PCR (qPCR).

RESULT(1) Stained by HE, lungs of experimental group showed destroyed alveoli, alveoli fusion and increased septal wall thickness, RAC were significantly lower than those in control group(14 d: septal wall thickness (12.69 ± 0.63) μm vs. (6.53 ± 0.16) μm, RAC 5.9 ± 0.4 vs. 8.4 ± 1.0, t = 19.046, 4.760, P both = 0.000). (2) CD31 protein was expressed predominantly in cytoplasm of pulmonary microvascular endothelial cells. The experimental group CD31 average optical density (AIOD) were decreased compared with control group((16.6 ± 1.6) × 10(3) vs.(40.1 ± 2.4) × 10(3), (18.1 ± 1.4) × 10(3) vs.(83.2 ± 5.2) × 10(3), (49.2 ± 5.4) × 10(3) vs.(136.2 ± 28.1) × 10(3), t=16.185, 16.066 and 6.078, P<0.01 for all comparisons). Capillary density in experimental group was also significantly decreased compared with control group ((3.84 ± 0.15)% vs.(6.01 ± 0.22)%, (4.17 ± 0.38)% vs.(6.15 ± 0.24)%, (5.43 ± 0.44)% vs. (9.13 ± 0.25)%, t = 16.124, 8.773 and 14.076, P all < 0.01). (3)RT-qPCR and Western blotting showed that the CASZ1 mRNA significantly increased in experimental group compared with control group(0.56 ± 0.17 vs. 1.00 ± 0.26, 0.32 ± 0.29 vs. 0.58 ± 0.14, 0.14 ± 0.22 vs. 0.56 ± 0.15, t=3.890, 3.303 and 2.388, P < 0.05 for all comparisons), and the protein expression of CASZ1 also significantly increased in experimental group compared with control group (0.65 ± 0.02 vs. 0.78 ± 0.23, 0.46 ± 0.03 vs. 0.75 ± 0.05, 0.34 ± 0.22 vs. 0.75 ± 0.04, t=6.200 and 10.485 and 14.998, P < 0.05 for all comparisons). (4)The protein level of CASZ1 in experimental group was positively correlated with capillary density (r=0.519, P<0.01).

CONCLUSIONCASZ1 is involved in the whole process of newborn rats BPD and may be linked to pulmonary microvascular dysplasia.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; pathology ; Female ; Hyperoxia ; pathology ; Lung ; blood supply ; pathology ; Male ; Oxygen ; adverse effects ; Pulmonary Alveoli ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; metabolism

We reviewed the data of 38 neonates who died of respiratory failure. Paraffin sections of the autopsy lung samples were examined with HE staining or immunolabeling for CD34, CD68 and CK to observe the development of the pulmonary vessels and detect potential pulmonary vascular diseases (PVDs). Five cases were identified to have PVDs, including pulmonary hypertensive vascular remodeling in 3 cases and alveolar capillary dysplasia in 2 cases. The result indicated that PVD was one of the important reasons for respiratory failure in these neonates.
Death ; Humans ; Infant, Newborn ; Lung ; pathology ; Lung Diseases ; diagnosis ; Persistent Fetal Circulation Syndrome ; pathology ; Pulmonary Alveoli ; abnormalities ; pathology ; Respiratory Insufficiency ; mortality ; Vascular Diseases ; diagnosis ; Vascular Remodeling

OBJECTIVETo study the pathology, imaging and clinical features of a child with trisomy 21 syndrome associated interstitial lung disease.

METHODData of a case with trisomy 21 syndrome associated interstitial lung disease confirmed by lung imaging and pathology were collected, analyzed and the related reports in literature were reviewed.

RESULTThe patient was a one year and 7 months old boy who suffered from severe pneumonia and recurrent infection during his hospital stay. When his disease was stable, he did not have shortness of breath and cyanosis, but a chest computed tomography (CT) showed ground-glass opacity, regional emphysema, band-like change in lung parenchyma, which indicated interstitial lung diseases. Unequal air inflation in bilateral lungs and diffuse over-distension of peripheral air spaces in lung surface were seen through thoracoscope. Pathological examination indicated that alveolar, alveolar ducts and alveolar sac were enlarged, alveolar septa was expanded. There were two reports in lung pathology of trisomy 21 syndrome, alveolar growth abnormalities was seen in 86%-88% cases. The multiple subpleural cysts in chest CT was characteristic. Clinically, trisomy 21 syndrome had high morbidity of respiratory tract infection and progress to respiratory failure frequently. Prolonged postoperative desaturation was constant which required long duration of respiratory support.

CONCLUSIONTrisomy 21 syndrome associated alveolar growth abnormalities were confirmed, which manifest as alveolar simplification in pathology and interstitial lung diseases in imaging. The risk of respiratory failure in these cases caused by infection and surgery should be considered.

Cysts ; pathology ; Down Syndrome ; complications ; Humans ; Infant ; Lung ; pathology ; Lung Diseases, Interstitial ; diagnosis ; etiology ; Male ; Postoperative Period ; Pulmonary Alveoli ; pathology ; Respiratory Insufficiency ; Respiratory Tract Infections ; Tomography, X-Ray Computed

OBJECTIVETo investigate the effect of arginine vasopressin (AVP) on alveolar fluid clearance (AFC) in acute lung injury (ALI).

METHODSForty-eight healthy adult Sprague-Dawley rats were randomly divided into control group, ALI model group and AVP treatment group. The pathological changes in the lungs, lung water content, alveolar permeability and AFC were observed, and the expressions of alveolar epithelial sodium channel (ENaC) and Na⁺, K⁺-ATPase were measured.

RESULTSCompared with those in the model group, the rats treated with AVP showed significantly decreased alveolar permeability (0.27 ± 0.15 vs 0.59 ± 0.19) and lung water content (5.01 ± 1.59 vs 8.67 ± 1.79) (P<0.05) and increased AFC (23.56 ± 4.51 vs 8.28 ± 3.57) and of α-ENaC expressions (1.296 ± 0.322 vs 0.349 ± 0.141) and α1-Na⁺, K⁺-ATPase (1.421 ± 0.389 vs 0.338 ± 0.186) (P<0.05).

CONCLUSIONAVP can promote AFC in with ALI possibly by up-regulation of α-ENaC, α1-Na⁺, and K⁺-ATPase.

Acute Lung Injury ; drug therapy ; Animals ; Arginine Vasopressin ; pharmacology ; Epithelial Sodium Channels ; metabolism ; Lung ; drug effects ; pathology ; Pulmonary Alveoli ; drug effects ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; metabolism

Fetal lung development normally occurs in a hypoxic environment. Hypoxia-inducible factor (HIF)-1alpha is robustly induced under hypoxia and transactivates many genes that are essential for fetal development. Most preterm infants are prematurely exposed to hyperoxia, which can halt hypoxia-driven lung maturation. We were to investigate whether the HIF-1alpha inducer, deferoxamine (DFX) can improve alveolarization in a rat model of bronchopulmonary dysplasia (BPD). A rat model of BPD was produced by intra-amniotic lipopolysaccharide (LPS) administration and postnatal hyperoxia (85% for 7 days), and DFX (150 mg/kg/d) or vehicle was administered to rat pups intraperitoneally for 14 days. On day 14, the rat pups were sacrificed and their lungs were removed and examined. A parallel in vitro study was performed with a human small airway epithelial cell line to test whether DFX induces the expression of HIF-1alpha and its target genes. Alveolarization and pulmonary vascular development were impaired in rats with BPD. However, DFX significantly ameliorated these effects. Immunohistochemical analysis showed that HIF-1alpha was significantly upregulated in the lungs of BPD rats treated with DFX. DFX was also found to induce HIF-1alpha in human small airway epithelial cells and to promote the expression of HIF-1alpha target genes. Our data suggest that DFX induces and activates HIF-1alpha, thereby improving alveolarization and vascular distribution in the lungs of rats with BPD.
Animals ; Bronchopulmonary Dysplasia/*drug therapy/*metabolism/pathology ; Deferoxamine/*administration & dosage ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism ; Male ; Pulmonary Alveoli/drug effects/*growth & development/metabolism/pathology ; Pulmonary Veins/drug effects/*growth & development/pathology ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome ; Up-Regulation/drug effects

OBJECTIVETo establish an animal model of sulfur mustard (SM)-induced acute lung injury in rats through different routes and compare the morphological changes in lung tissue and cells.

METHODSOne hundred and thirty-six male rats were selected and randomly divided into 5 groups, namely peritoneal cavity SM group (n=32), trachea SM group (n=32), peritoneal cavity propylene glycol group (n=32), trachea propylene glycol group (n=32), and normal control group (n=8). The rats in peritoneal cavity SM group were injected intraperitoneally with diluted SM (0.1 ml, 8 mg/kg), and the rats in trachea SM group were injected intratracheally with diluted SM (0.1 ml, 2 mg/kg). Once the rats were sacrificed at 6, 24, 48, and 72 h after SM treatment, morphological changes in lung tissue and cells were observed by light and electron microscopy.

RESULTSIn the peritoneal cavity SM group, the epithelial cells of bronchioles maintained intact with increased exudate and bleeding in alveolar cavity and large areas of pulmonary consolidation under the light microscope. In the tracheal SM group, focal ulcer formed in the epithelial cells of bronchioles with increased exudate and bleeding in alveolar cavity, partial pulmonary consolidation, and compensatory emphysema in peripheral alveolar space under the light microscope. The alveolar interval areas were widened obviously in both groups in a time-dependent manner. Under the electron microscope, we observed local loss of cellular membrane in type I alveolar epithelium, broken or lost microvilli in cells of typeⅡalveolar epithelium and fuzzy mitochondrial crista as well as the appearance of ribosome detached from rough endoplasmic reticulum in both two groups. Compared with those in the trachea SM group and the control group, the ratio of the alveolar septum average area to the visual field area in the peritoneal cavity SM group at 6, 24, 48, and 72 h was significantly higher (P<0.05).

CONCLUSIONThe lung tissue injury through the intraperitoneal route is more severe than that through the tracheal route, while focal ulceration of bronchioles epithelial cells appears in the case of tracheal route. The degree of injury increases over time in both groups, and the cellular damage is approximately the same in both groups.

Acute Lung Injury ; chemically induced ; pathology ; Animals ; Disease Models, Animal ; Lung ; pathology ; Male ; Mustard Gas ; toxicity ; Peritoneum ; Pulmonary Alveoli ; pathology ; ultrastructure ; Rats ; Trachea

ATP-Binding Cassette Transporters ; genetics ; DNA Mutational Analysis ; Humans ; Infant ; Lung ; pathology ; physiopathology ; Lung Diseases, Interstitial ; diagnosis ; genetics ; pathology ; Mutation ; genetics ; Pulmonary Alveoli ; pathology ; Pulmonary Surfactant-Associated Proteins ; deficiency ; genetics