Dataset Information

Potential mechanism and key genes involved in mechanical ventilation and lipopolysaccharide-induced acute lung injury

ABSTRACT: Mechanical ventilation (MV) and lipopolysaccharide (LPS) infection are common causes of acute lung injury. The aim of the present study was to identify the key genes and potential mechanisms involved in mechanical ventilation (MV) and lipopolysaccharide (LPS)-induced acute lung injury (ALI). Gene expression data of adult C57BL/6 mice with ALI induced by inhaling LPS, MV and LPS + MV were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) associated with MV, LPS and LPS + MV were screened, followed by functional enrichment analysis, protein-protein interaction network construction, and prediction of transcription factors and small molecule drugs. Finally, the expression of key genes was verified in vivo using reverse transcription-quantitative PCR. A total of 63, 538 and 1,635 DEGs were associated with MV, LPS and LPS + MV, respectively. MV-associated genes were significantly enriched in the ‘purine ribonucleotide metabolic process’. LPS and LPS + MV-associated genes were significantly enriched in ‘cellular response to cytokine stimulus’ and ‘cell chemotaxis’. All three conditions were enriched in ‘TNF signaling pathway’ and ‘IL-17 signaling pathway’. Expression levels of C-X-C motif chemokine ligand (CXCL)2, CXCL3 and CXCL10 were upregulated in the LPS and LPS + MV groups. Adenosine A2b receptor, zinc finger and BTB domain-containing 16 and hydroxycarboxylic acid receptor 2 were identified as DEGs in the MV group. Compared with the control group, Early growth response 1 and activating TF 3 was upregulated in all three groups. Similarities and differences were observed among the MV- and LPS-induced ALI, and MV may enhance the effects of LPS on gene expression. MV may affect urine ribonucleotide metabolic-related processes, whereas LPS may cause cell chemotaxis and cytokine stimulus responses in ALI progression. The inflammatory response was shared by MV and LPS. The results of the present study may provide insight into a theoretical basis for the study and treatment of ALI.

SUBMITTER: Dong W

PROVIDER: S-EPMC7533521 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundSurvival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); however, the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention.MethodsWe randomly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). The primary end point was improvement in oxygenation. The secondary end points included respiratory-system compliance and patient outcomes.ResultsThe study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided group than in the control group (95% confidence interval, 78.1 to 98.3; P=0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P=0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P=0.01 by repeated-measures analysis of variance).ConclusionsAs compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

Project description:ObjectivesTo provide proof-of-concept for a protocol applying a strategy of personalized mechanical ventilation in children with acute respiratory distress syndrome. Positive end-expiratory pressure and inspiratory pressure settings were optimized using real-time electrical impedance tomography aiming to maximize lung recruitment while minimizing lung overdistension.DesignProspective interventional trial.SettingTwo PICUs.PatientsEight children with early acute respiratory distress syndrome (< 72 hr).InterventionsOn 3 consecutive days, electrical impedance tomography-guided positive end-expiratory pressure titration was performed by using regional compliance analysis. The Acute Respiratory Distress Network high/low positive end-expiratory pressure tables were used as patient's safety guardrails. Driving pressure was maintained constant. Algorithm includes the following: 1) recruitment of atelectasis: increasing positive end-expiratory pressure in steps of 4 mbar; 2) reduction of overdistension: decreasing positive end-expiratory pressure in steps of 2 mbar until electrical impedance tomography shows collapse; and 3) maintaining current positive end-expiratory pressure and check regional compliance every hour. In case of derecruitment start at step 1.Measurements and main resultsLung areas classified by electrical impedance tomography as collapsed or overdistended were changed on average by -9.1% (95% CI, -13.7 to -4.4; p < 0.001) during titration. Collapse was changed by -9.9% (95% CI, -15.3 to -4.5; p < 0.001), while overdistension did not increase significantly (0.8%; 95% CI, -2.9 to 4.5; p = 0.650). A mean increase of the positive end-expiratory pressure level (1.4 mbar; 95% CI, 0.6-2.2; p = 0.008) occurred after titration. Global respiratory system compliance and gas exchange improved (global respiratory system compliance: 1.3 mL/mbar, 95% CI [-0.3 to 3.0], p = 0.026; Pao2: 17.6 mm Hg, 95% CI [7.8-27.5], p = 0.0039; and Pao2/Fio2 ratio: 55.2 mm Hg, 95% CI [27.3-83.2], p < 0.001, all values are change in pre vs post).ConclusionsElectrical impedance tomography-guided positive end-expiratory pressure titration reduced regional lung collapse without significant increase of overdistension, while improving global compliance and gas exchange in children with acute respiratory distress syndrome.

Dataset Information

Potential mechanism and key genes involved in mechanical ventilation and lipopolysaccharide-induced acute lung injury

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets