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 investigate the protective effect and mechanism of curcumin on lipopolysaccharide (LPS)-induced acute lung injury.MethodsTotally 24 SD rats were randomly divided into a control group, a LPS group and a LPS+curcumin group (n=8 in each group). The degree of lung injury (oxygen partial pressure, wet/dry ratio, pathological scores) and inflammatory levels [tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, Toll-like receptor 4 (TLR4), mobility group box 1 protein (HMGB1) expression] of the lung were detected in different groups.ResultsOxygen partial pressure was significantly lower in the LPS group than that in the control group (P<0.05), while wet/dry ratio, pathological scores and expression levels of TNF-α, IL-6, MCP-1, TLR4 and HMGB1 were significantly higher in the LPS group than those in the control group (P<0.05). Compared with the LPS group, curcumin significantly reduced wet/dry ratio, pathological scores and expression levels of TNF-α, IL-6, MCP-1, TLR4 and HMGB1 in the LPS+curcumin group (P<0.05), while it significantly improved oxygen partial pressure (P<0.05).ConclusionCurcumin might protect LPS-induced acute lung injury through inhibition of TLR4-HMGB1-inflammation pathway.
Objective To investigate the role of angiotensin-II type 1 receptor ( AT1) antagonist in treatment of acute lung injury/acute respiratory distress syndrome ( ALI/ARDS) . Methods Animal model of ALI/ARDS was induced by cecal ligation and perforation ( CLP) . ALI/ARDS animals received a separate intraperitoneal injection of several concentrations( 5, 10, 15, 20, 25 mg/kg) of AT1 inhibitor losartan after CLP, then the changes of lung injury and 7-day survival were measured. Results Oxygenation index and lung wet to dry weight ratio ( W/D) showed an improving trend when losartan was administered at doses of 5 to 15 mg/kg in ALI/ARDS rats, but aggravated above the dose of 15 mg/kg. Losartan ( 15 mg/kg) treatment significantly alleviated pulmonary edema after CLP operation, and decreased serumlevels of TNF-α, IL-6, andIL-1β [ TNF-α: ( 554. 1 ±62. 7 ) pg/mL vs. ( 759. 2 ±21. 5 ) pg/mL, P lt; 0. 01; IL-6: ( 1227. 3 ±130. 0) pg/mL vs. ( 2670. 4 ±174. 1) pg/mL, P lt; 0. 01; IL-1β: ( 444. 0 ±38. 6) pg/mL vs. ( 486. 6 ±61. 7)pg/mL, P lt; 0. 05] . 7-day survival rate also increased in losartan treatment group at a dose of 15 mg/kg( 6. 7% vs. 0 ) . Conclusions The AT1 inhibitor, losartan, can significantly prevent lung injury in ALI/ARDS after CLP, and improve the 7-day survival rate.
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.
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 effects of mechanical ventilation( MV) via different tidal volume ( VT) in combination with positive end expiratory pressure( PEEP) on dogs with acute lung injury( ALI) . Methods Dog model of oleic acid-induced ALI was established. And after that animals were randomized into different MV groups ( included low VT group, VT =6 mL/kg; and high VT group, VT =20 mL/kg) and ventilated for 6 h with a PEEP of 10 cmH2O. Arterial blood gas wasmeasured before, during and after ALI model was established ( at 1 h,2 h, 4 h and 6 h during MV) . The albumin concentration in BALF and pathological change of the lung tissue were evaluated in order to determine the lung injury while animals were sacrificed after 6 h MV. Results ALI model was successfully established ( 2. 50 ±0. 80) hours after oleic acid injection. Arterial pH decreased much severer in the low VT group than the high VT group( P lt;0. 01) . PaO2 and SaO2 in ventilation groups decreased after modeling but increased after MV, and PaO2 and SaO2 were significantly higher in the low VT group than the high VT group after 6 h MV( P lt;0. 05) . PaCO2 fluctuated less in the high VT group, while it increased significantly in the low VT group after MV( P lt; 0. 01) . Oxygenation index( PaO2 /FiO2 ) was lowered after modeling( P lt; 0. 01) , decreased to about 190 mm Hg after 1 h MV. And PaO2 /FiO2 in low VT group was significantly higher than the high VT group after 6 h MV( P lt; 0. 05) . BALF albumin concentration and the lung injury score in the low VT group were both significantly lower than the high VT group( both P lt; 0. 05) . Conclusions Ventilation with PEEP could improve the oxygenation of ALI dogs, and low VT ventilation improves the oxygenation better than high VT. Otherwise, low VT could induce hypercapnia and ameliorate lung injury caused by high VT MV.
ObjectiveTo investigate the role and mechanism of P-selectin glycoprotein ligand-1 (PSGL-1) in hydrochloric acid-induced acute lung injury (ALI) in mice.MethodsWild-type mice (WT) and PSGL-1 knockout mice (PSGL-1 -/-) were randomly subjected to normal saline (NS) or hydrochloric acid (HCl) challenged group. The mice were intratracheally instilled with NS or HCl (1 μl/g weight) into the left lung with a catheter. After 2 hours, respiratory function index enhanced pause (Penh), PaO2 and PaO2 were analyzed. The wet to dry weight ratio (W/D) of the left lung and total protein concentration in bronchoalveolar lavage fluid (BALF) were measured. The number of leukocytes in BALF was counted too. Targeted lung tissue was processed for further HE or immunohistochemistry staining. Meanwhile, the expressions of interleukin-6 (IL-6), IL-1β, nuclear factor-κB (NF-κB), IκBa and p-IκBa in lung tissue were measured.ResultsThe Penh (4.77±1.22 vs. 5.80±0.84) and PaCO2 [(63.7±3.9) mm Hg vs. (74.4±7.4) mm Hg] in the PSGL-1 knockout mice were significantly lower than those in the WT mice after HCl stimulation (P<0.05), while the PaO2 was higher than that in the WT mice [(81.0±7.1) mm Hg vs. (62.0±8.9) mm Hg, P<0.05)]. The lung W/D ratio (4.86±0.15 vs. 5.22±0.20), protein concentration [(3.71±0.64) μg/μl vs. (4.74±0.98) μg/μl] and total leukocyte count [(13.00±2.18) ×107/L vs. (49.42±3.35) ×107/L] in BALF were significantly lower in the PSGL-1 knockout mice challenged with HCl than those in the WT mice (P<0.05). Besides, the protein expressions of IL-6, IL-1β, p65 and p-IκBa in the PSGL-1 knockout mice were lower than those in the WT mice after HCl instillation, while the IκBa expression was higher than that in the WT mice (P<0.05). More numbers of neutrophils and macrophages were found in the lung of the WT mice than the PSGL-1 knockout mice challenged with HCl. However, the differences of above values between the WT mice and the PSGL-1 knockout mice instilled with NS were not found, all of which were significantly lower than the correspongding HCl group except for IκBa (P<0.05).ConclusionPSGL-1 may play important roles in the development of HCl-induced ALI via the NF-κB signaling pathway and inflammation.
Objective To investigate the possible role of ulinastatin(UTI) in f lipopolysacccharide (LPS)-induced acute lung injury(ALI).Methods Thirty male SD rats were randomly divided into three groups，ie.a normal control group，a LPS group and a LPS plus UTI group.The rats were injected with 1 mL of normal saline via caudal vein in the control group，with LPS 5 mg/kg via caudal vein in the LPS group，and with UTI 100000 U/kg shortly after injection with LPS in the LPS plus UTI group.The rats were sacrificed 4 h after the injection.Lung wet/dry weight ratio was measured.IL-18 level in serum and lung tissue was determined by ELISA and the expression of NF-κB in lung tissue was determined by immunohistochemistry.Pathological changes of rats’ lung were observed by optical and electron microscope.Results Compared with the control group，IL-18 level in serum and NF-κB expression in lung tissue were significantly higher in the LPS group(Plt;0.01).The IL-8 level was somewhat elevated in the LPS+UTI group but with no significant difference from that in control group was found (Pgt;0.05).The lung inflammation in the LPS+UTI group was milder than that in the LPS rats.Conclusion UTI can alleviate LPS-induced inflammatory reaction and lung injury in rat model.
Objective To explore the effects of different humidification and heating strategies during non-invasive positive pressure ventilation( NIPPV) in patients with ALI/ARDS. Methods A total of 45 patients with ALI/ARDS were randomly divided into three groups to receive NIPPV with different humidification and heating strategies, ie. Group A ( humidification with a 370 Humidifier without heating) ,group B ( humidification with a 370 Humidifier along with a MR410 Heater) , and group C ( humidification and heating with aMR850 Humidifier, and a RT308 circuit heater) . The changes of air temperature, absolute humidity, relative humidity, sputum thickness and patient comfort were compared between the three groups. Sputum thickness was evaluated with AWSS scoring system. Results After humidification and heating, the air temperature, absolute humidity and AWSS score improved significantly in group B [ elevated from ( 23. 9 ±1. 0) ℃, (9.8 ±1. 3) mg/L and 2. 0 ±0. 7 respectively to ( 30. 3 ±1. 7) ℃, ( 31. 0 ±2. 3)mg/L and ( 3. 0 ±0. 9) respectively, P lt; 0. 001] and group C [ elevated from( 23. 8 ±1. 0) , ( 9. 8 ±1. 5)mg/L and ( 2. 1 ±0. 7) respectively to ( 34. 0 ±1. 1) ℃, ( 43.8 ±2. 5) mg /L and 3. 5 ±1. 0 respectively,P lt; 0. 001] . Air temperature and absolute humidity were significantly higher in group C than those in group B( P lt; 0. 001) . Of all the parameters, only absolute humidity showed a significant improvment in group A [ elevated from( 9. 9 ±1. 6) mg/L to ( 11. 9 ±0. 9) mg/L, P lt; 0. 001] . The degree of comfort in group C was significantly higher than that in group A and B [ 8. 0 ±1. 7 vs 5. 0 ±1. 2 and 3. 0 ±0. 4, respectively, P lt;0. 001] . In group A seven patients were switched to group C because of discomfort, four accepted NIPPV continuously, and two avoided invasive mechanical ventilation eventually. In group B three patients were switched to group C because of intolerance of too much condensed water in the breathing circuit, all of them accepted NIPPV continuously, and one avoided invasive mechanical ventilation eventually. Conclusions Compared with mere humidification or humidification with heating humidifier, humidification with heating humidifier and circuit heating during NIPPV can improve the absolute humidity, air temperature and patient comfort,meanwhile decreasing the sputumthickness of patients with ALI/ARDS.
Objective To investigate the expression of granulysin ( GNLY) in lung of rats with acute lung injury ( ALI) stimulated with lipopolysaccharide ( LPS) . Methods Thirty-six healthy adult Wistar rats were randomly divided into a normal control group and a LPS group, with 18 rats in each group. LPS ( 4 mg/kg) was given intraperitoneally in the LPS group to induce ALI. The same amount of normal saline was given in the control group. The rats were randomly assigned to three subgroups ( n = 6) to be sacrificed respectively at 6, 18, and 30 hours after intraperitoneal injection. Wet/dry lung weight ratio ( W/D) and pathological changes of the lung were observed. The expression of GNLY in lung tissue was assayed by immunohistochemistry. Results In the LPS group, the W/D ratio was higher than that of the control group at each time point ( P lt;0. 05) and there were a large number of inflammatory cells infiltration and edema in interstitial spaces which suggested ALI. Compared with the control group, the expression of GNLY in the LPS group was significantly increased at all time points ( P lt;0. 05) . Conclusion GNLY may participate in ALI inflammatory process, which might play a role in preventing infection induced ALI.