Objective To explore the protective effects of liver X receptor-αactivator ( LXRα)T0901317 on rats with acute lung injury ( ALI) . Methods Seventy-two male Wistar rats were randomly divided into three goups, ie. a control group, a LPS group, and a T0901317 group. Artery blood gas analysis,lung tissue wet/dry weight ratio,myeloperoxidase activity, and lung histopathological changes were measured.The expressions of LXRαand TNF-αmRNA in lung tissue were detected by RT-PCR. The protein levels ofTNF-αand LXRαwere examined with ELISA and immunohistochemistry, respectively. Results In the ALI rats, PaO2 decreased, lung W/D weight ratio and myeloperoxidase activity increased significantly compared with the control group ( P lt; 0. 05) . Histopathological examination also revealed obvious lung injury. In theLPS group, the expression of TNF-αmRNA in lung tissue and the level of TNF-αprotein in lung homogenate and serum increased markedly( all P lt; 0. 05) while the expression of LXR-αmRNA declined significantly ( P lt; 0. 05) . Immunohistochemical staining showed that lung tissues of the normal rats expressed LXRαsignificantly but in the LPS group the expression of TNF-αand LXR-αin lung tissue decreased markedly ( P lt;0. 05) . After the treatment with T0901317, the expressions of LXR-αin lung tissues were significantly higher than those in the LPS group both at the mRNA and the protein level ( P lt; 0. 05) . Conclusion T0901317 plays an anti-inflammatory effect through up-regulating the expression of LXR-αand suppressing the expression of TNF-α, thus reduces the infiltration and aggregation of inflammatory cells in lung tissue.
【Abstract】Objective To investigate the role of VEGF and its soluble VEGF receptor ( sVEGFR-1) in pathogenesis of acute lung injury ( ALI) induced by immersion in seawater after open chest trauma. Methods Sixteen hybridized adult dogs were randomly divided into control group and seawater group. The control group only suffered from open chest trauma, whereas the seawater group were exposed to seawater after open chest trauma. Blood samples were collected at the 0, 2, 4, 6, 8 h after trauma for measurement of white blood cell count, arterial blood gas, plasma osmotic pressure ( POP) , electrolyte concentration, IL-8, vWF, VEGF and sVEGFR-1 levels. The lungs tissue and BALF was collected at 8 h after trauma. Pathological changes of the lung was observed under light microscope by HE staining. Meanwhile VEGF and sVEGFR-1 levels were measured in BALF and lung tissue homogenate. Total protein concentrations in plasma and BALF were measured to calculate the pulmonary penetration index ( PPI) . Results The lung of the seawater group showed interstitial mononuclear cell and neutrophil infiltration, interstitial edema, and vascular congestion. VEGF and sVEGFR-1 were significantly increased in the plasma, while VEGF was significantly reduced in the lung tissues and BALF. The levels of IL-1β, IL-8 and vWF, just as the level of VEGF, were significantly increased in the plasma. Meanwhile, the POP and electrolyte concentration were significantly increased. In the plasma, the responses of VEGFs during the early onset of ALI induced by immersion in seawater after open chest trauma were consistent with the POP and PPI. Conclusions High plasma levels and low BALF/ lung tissue levels of VEGFs is a distinguishing characteristic during the early onset of ALI induced by immersion in seawater after open chest trauma. VEGF may be a novel biomarker which has an important role in the development of ALI.
ObjectiveTo explore the role of osteopontin (OPN) in hyperoxia-induced acute lung injury and its relationship with nuclear factor-κB (NF-κB),matrix metalloproteinase 2 and 9 (MMP-2,MMP-9). MethodsNinety-six mice were randomly divided into a phosphate buffer solution intranasal inhalation group (PBS group) and a recombinant OPN intranasal inhalation group. The mice were exposed in sealed cages >95% oxygen for 24-72 hours to induce lung injury or room air as control. The severity of lung injury was evaluated. The expression of NF-κB,MMP-2,MMP-9,TIMP-1 and TIMP-2 mRNA in lung tissue at 24,48 and 72 hours under hyperoxia were examined by reverse transcript-polymerase chain reaction (RT-PCR). Immunohistochemistry (IHC) was performed for detection of NF-κB protein in lung tissue. ResultsPBS group mice developed more severe acute lung injury at 72 hours under hyperoxia.TIMP-1 and TIMP-2 mRNA expressions were significantly increased in r-OPN group than their matched PBS group when exposed to hyperoxia. IHC study showed higher expression of NF-κB protein in lung tissue of PBS group at 72 hours of hyperoxia. ConclusionOPN can protect against hyperoxia-induced lung injury by inhibiting the expressions of NF-κB,MMP-2 and MMP-9.
With the growth of offshore activities, the incidence rates of seawater drowning (SWD) induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) increase significantly higher than before. Pulmonary interstitial edema, alveolar septum fracture, red blood cells, and inflammatory cells infiltration can be seen under light microscope in the pathologic changes of lungs. The major clinical manifestations are continual hyoxemia and acidosis, which lead to a severe condition, a high death rate, and a poor treatment effect. Bone marrow mesenchymal stem cells are capable of self-renewal, multilineage differentiation and injured lung-homing, which are induced to differentiate into alveolar epithelial cells and pulmonary vascular endothelial cells for tissues repairing. This may be a new way to treat SWD-ALI and SW-ARDS.
Ojective To establish a rat model of hyperoxia induced acute lung injury. Methods Eighty healthy male SD rats were randomly divided into an air group and a hyperoxia group ( ≥95% O2 ) .Each group was further divided into 12 h, 24 h, 36 h, 48 h, 60 h subgroups. Arterial blood gas was monitored. Lung tissue was sampled for evaluation of lung wet to dry ratio, lung index, and pulmonary permeation index. Bronchoalveolar lavage fluid ( BALF) was collected for measurement of lactatedehydrogenase ( LDH) activity and white blood cell count ( WBC) . Results After hyperoxia exposure for 48 ～60 h, lung pathology showed alveolar structure disruption, lung parenchyma wrath bleeding and edema.Lung wet to dry ratio, lung index, pulmonary permeation index, LDH and WBC in BALF all increased significantly, peaked at 48 h and remained at high level at 60 h while PaO2 dropped progressively.Conclusion Exposure to ≥ 95% O2 for 48 ～60 h can successfully establish the rat model of hyperoxia induced acute lung injury.
ObjectiveTo explore the mechanism of lung injury in Sprague-Dawley (SD) rats induced by acute organic phosphorus pesticides (AOPP) by observing the changes of the blood serum nuclear factor (NF)-κB consistence, NF-κB level of lung tissue and lung coefficient. MethodNinety-six healthy male SD rats (six weeks old) were randomly divided into group A (control, n=48) and group B (poison, n=48). The rats of group B were given omethoate by gavage (45 mg/kg), and the rats of group A accepted normal saline. Then the rats were killed at designated observing points (30 minutes; 3, 6, 12, 24, and 48 hours), and the lung coefficient, blood serum NF-κB consistence and NF-κB level of lung tissue were measured. At the same time, we observed the pathological changes of the rats' lung tissue. ResultsCompared with group A, blood serum NF-κB consistence, NF-κB level of lung tissue and the level of lung coefficient in group B were significantly higher (P<0.01). The lung tissues of group A were normal at each time point, but in group B, the lung pathological changes gradually appeared 30 minutes later with pulmonary interstitial engorging, alveolar septum widening and some alveolus being full of red blood cells, and this situation reached its peak at hour 12. Then it gradually mitigated from 24 to 48 hours. ConclusionThere are significant increases in blood serum NF-κB consistence and NF-κB level in lung tissues in rats with lung injury induced by omethoate poisoning. The NF-κB may play a role in the process of lung injury induced by organophosphorus pesticide.
Objective To investigate the mechanismof lung injury caused by paraquat poisoning by observing the changes of fibrogenic cytokines in acute paraquat poisoned rats and the effects of pyrrolidine dithiocarbamate ( PDTC) . Methods Sprague-Dawley rats were randomly divided into three groups, ie. acontrol group ( n =6) , a PDTC group ( n =36) , a paraquat group ( n = 36) , and a paraquat + PDTC group( n =36) . The rats in the PDTC group, the paraquat group, and the paraquat + PDTC group were subdivided into 6 subgroups sacrificed respectively on 1st, 3rd,7th,14th, 28th and 56th day after the treatment. The levels of transforming growth factor-β1( TGF-β1 ) , platelet-derived growth factor ( PDGF) , insulin-like growthfactor-1 ( IGF-1) in serum were measured. Meanwhile the expression of connective tissue growth factor ( CTGF) and hydroxyproline in lung tissues were detected. The relationship of above cytokines with hydroxyproline was analyzed. Results The destructive phase in early ( 1 ～7 d) was characterized by hemorrhage, alveolar edema, and inflammatory cell infiltration. The proliferous phase in later stage ( 14 ～56 d) was characterized by diffused alveolar collapse with fibroblast proliferation and patchy distribution of collagen fibers. Compared with the control group, the level of TGF-β1 on all time points, the level of PDGF from7th to 56th day, the level of IGF-1 from3rd to 56th day in the paraquat group all significantly increased ( P lt;0. 01) . Immunohistochemistry results showed CTGF positive cells mainly located in aleolar epithelialcells, endothelial cells,macrophages in early stage, and fibroblasts were main positive cells on the 28th and the 56th day. The expression of CTGF in the paraquat group increased gradually compared with the control group on different time points ( P lt; 0. 05 or P lt; 0. 01) . Meanwhile, the levels of above cytokines were positively correlated with the level of hydroxyproline. Noteworthy, PDTC treatment led to significant decreases of above cytokines compared with the paraquat group in corresponding time points ( P lt;0. 05 or P lt;0. 01) .Conclusions Over expressions of IGF-1, TGF-β1 , PDGF, IGF-1 and CTGF may play important roles in lung fibrosis of paraquat poisoned rats. PDTC, as a b NF-κB inhibitor, may inhibits NF-κB activity and further significantly decreases expressions of cytokines, leading to significantly attenuated pulmonary inflammation and fibrosis. However, the mechanisms of PDTC intervention still remain to be explored.
ObjectiveTo analyze the effect of noninvasive positive pressure ventilation (NPPV) on the treatment of severe acute pancreatitis (SAP) combined with lung injury [acute lung injury (ALI)/acute respiratory distress syndrome (ARDS)] in emergency treatment. MethodsFifty-six patients with SAP combined with ALI/ARDS treated between January 2013 and March 2015 were included in our study. Twenty-eight patients who underwent NPPV were designated as the treatment group, while the other 28 patients who did not undergo NPPV were regarded as the control group. Then, we observed patients' blood gas indexes before and three days after treatment. The hospital stay and mortality rate of the two groups were also compared. ResultsBefore treatment, there were no significant differences between the two groups in terms of pH value and arterial partial pressure of oxygen (PaO2) (P>0.05). Three days after treatment, blood pH value of the treatment group and the control group was 7.41±0.07 and 7.34±0.04, respectively, with a significant difference (P＜0.05); the PaO2 value was respectively (60.60±5.11) and (48.40±3.57) mm Hg (1 mm Hg=0.133 kPa), also with a significant difference (P＜0.05). The hospital stay of the treatment group and the control group was (18.22±3.07) and (23.47±3.55) days with a significant difference (P＜0.05); and the six-month mortality was 17% and 32% in the two groups without any significant difference (P>0.05). ConclusionIt is effective to treat patients with severe acute pancreatitis combined with acute lung injury in emergency by noninvasive positive pressure ventilation.
Objective To identify genes of lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice base on bioinformatics and machine learning. Methods The acute lung injury dataset (GSE2411, GSE111241 and GSE18341) were download from the Gene Expression Database (GEO). Differential gene expression analysis was conducted. Gene ontology (GO) analysis, KEGG pathway analysis, GSEA enrichment analysis and protein-protein interaction analysis (PPI) network analysis were performed. LASSO-COX regression analysis and Support Vector Machine Expression Elimination (SVM-RFE) was utilized to identify key biomarkers. Receiver operator characteristic curve was used to evaluate the diagnostic ability. Validation was performed in GSE18341. Finally, CIBERSORT was used to analyze the composition of immune cells, and immunocorrelation analysis of biomarkers was performed. Results A total of 29 intersection DEGs were obtained after the intersection of GSE2411 and GSE111241 differentially expressed genes. Enrichment analysis showed that differential genes were mainly involved in interleukin-17, cytokine - cytokine receptor interaction, tumor necrosis factor and NOD-like receptor signaling pathways. Machine learning combined with PPI identified Gpx2 and Ifi44 were key biomarkers. Gpx2 is a marker of ferroptosis and Ifi44 is an type I interferon-induced protein, both of which are involved in immune regulation. Immunocorrelation analysis showed that Gpx2 and Ifi44 were highly correlated with Neutrophils, TH17 and M1 macrophage cells. Conclusion Gpx2 and Ifi44 have potential immunomodulatory abilities, and may be potential biomarkers for predicting and treating ALI in mince.
ObjectiveTo study the protective effect and mechanism of ophiopogonin D (OP-D) on lipopolysaccharide induced acute lung injury (ALI) in mice.MethodsFifty SPF C57BL/6 mice were randomly divided into five groups, ie. a control group, a sham operation group, a model group, an OP-D group (10 mg·kg–1·d–1), and a dexamethasone group (2 mg·kg–1·d–1), with 10 mice in each group. One day before the establishment of the model, the OP-D group and the dexamethasone group received the corresponding drugs by gavage. The model group, the OP-D group and the dexamethasone group received lipopolysaccharide (2 mg/kg, 30 μL) through the trachea to establish the ALI model. The sham operation group received the same volume of normal saline. The blank control group was not treated. Six hours after the operation, the mice were weighed and then killed for peripheral blood and lung tissue. The weight of lung tissue was measured to evaluate the degree of pulmonary edema; the pathological changes of lung tissue were observed by hematoxylin-eosin staining; the mRNA expressions of interleukin (IL)-6, IL-10, and IL-17 in lung tissue were detected by qPCR; the percentage of Th17 and Treg cells in peripheral blood was detected by flow cytometry.ResultsCompared with the model group, the degree of pulmonary edema in the OP-D group decreased significantly (P<0.05), the lung tissue injury decreased, the mRNA expressions of IL-6 and IL-17 in the lung tissue and the proportion of Th17 cells in the peripheral blood decreased significantly (P<0.05), the proportion of Treg cells in the peripheral blood and the mRNA expression of IL-10 in the lung tissue increased significantly (P<0.05).ConclusionOP-D may have therapeutic effect on LPS induced ALI in mice by regulating the balance of Th17/Treg cells.