MiR-9a-5p alleviates ventilator-induced lung injury in rats by inhibiting the activation of the MAPK signaling pathway via CXCR4 expression downregulation.

BACKGROUND: Globally, Mechanical ventilation is the most commonly used short-term life support technology. Ventilator-induced lung injury (VILI) is an inflammatory injury caused by mechanical ventilation. MicroRNAs (miRNAs) are considered as new gene regulators that play an important role in lung injury and inflammation. However, the role and mechanism of action of miR-9a-5p in VILI remain unclear. METHODS: Herein, a rat model of VILI was established. To determine the expression levels of miR-9a-5p and CXCR4 mRNA, real-time quantitative polymerase chain reactions (qRT-PCR) were conducted. As well as western blot (WB) and immunofluorescence analyses, we determined the expression of CXCR4, SDF-1 and MAPK signaling pathway-related kinases. Hematoxylin and eosin (H&E) staining and the wet-dry ratio of the lung tissue were used to evaluate organ injury. An enzyme-linked immunosorbent assay (Elisa) and myeloperoxidase (MPO) activity measurements were performed to evaluate the inflammatory response. In addition, double luciferase reporter assays were used to verify the association between miR-9a-5p and CXCR4. RESULTS: The expression of miR-9a-5p was low, whereas that of CXCR4 was high in the lung tissues of VILI rats. The overexpression of miR-9a-5p alleviated the degree of pathological injury in the lung tissues of rats with VILI, downregulating inflammatory cytokine expression and MPO activity. In the VILI rat model, miR-9a-5p targeted the negative regulation of CXCR4, and CXCR4 overexpression to reverse the lung-protective and anti-inflammatory effects of miR-9a-5p overexpression in VILI rats. miR-9a-5p also inhibited the phosphorylation of extracellular signal receptor-activated kinase (ERK), a protein related to the MAPK signaling pathway, by downregulating CXCR4 expression. CONCLUSION: miR-9a-5p can hinder the activation of the MAPK/ERK signaling pathway and reduce inflammatory reactions and lung injury in VILI rats through the targeted regulation of CXCR4 expression. Therefore, miR-9a-5p could serve as an intervention target to supply a new strategy for the care of VILI.

Biphasic positive airway pressure spontaneous breathing attenuates lung injury in an animal model of severe acute respiratory distress syndrome.

OBJECTIVE: To compare the effects of unassisted spontaneous breathing (SB) and complete muscle paralysis (PC) on early severe acute respiratory distress syndrome (ARDS) in an animal model, and to explore the possibility of biphasic positive airway pressure (BIPAP) as lung protective ventilation support for patients in the early stage of severe ARDS. METHODS: Twelve healthy beagle dogs between the ages of 10 and 15 months were randomly divided into two groups: the SB group (BIPAPSB) and the PC group (BIPAPPC). Arterial blood samples were drawn before modelling. Arterial blood gas analysis and mechanical tests were conducted. The animal model of severe ARDS was established using a deep intravenous injection of oleic acid, and BIPAP ventilation was performed for 8 hours. Lung tissue and blood were taken to detect lung function, inflammatory reactions and degree of pathological damage. RESULTS: At the beginning of the experiment, there was no significant difference in the arterial blood gas analysis between the two groups (p > 0.05). After successful modelling, the oxygenation index and the end-expiratory lung volume in the SB group were significantly higher than those in the PC group 8 hours after MV. Pathologically, the wet-dry ratio and pathological score of the PC group were higher than those of the SB group; the lung injury in the gravity-dependent area in the SB group was less than that in the PC group (p< 0.05). CONCLUSIONS: In the early stage of severe ARDS induced by oleic acid, compared with PC, retention of the BIPAP mode of SB can reduce the risk of lung injury and improve respiratory function.

c-Fos is a mechanosensor that regulates inflammatory responses and lung barrier dysfunction during ventilator-induced acute lung injury.

BACKGROUND: As one of the basic treatments performed in the intensive care unit, mechanical ventilation can cause ventilator-induced acute lung injury (VILI). The typical features of VILI are an uncontrolled inflammatory response and impaired lung barrier function; however, its pathogenesis is not fully understood, and c-Fos protein is activated under mechanical stress. c-Fos/activating protein-1 (AP-1) plays a role by binding to AP-1 within the promoter region, which promotes inflammation and apoptosis. T-5224 is a specific inhibitor of c-Fos/AP-1, that controls the gene expression of many proinflammatory cytokines. This study investigated whether T-5224 attenuates VILI in rats by inhibiting inflammation and apoptosis. METHODS: The SD rats were divided into six groups: a control group, low tidal volume group, high tidal volume group, DMSO group, T-5224 group (low concentration), and T-5224 group (high concentration). After 3 h, the pathological damage, c-Fos protein expression, inflammatory reaction and apoptosis degree of lung tissue in each group were detected. RESULTS: c-Fos protein expression was increased within the lung tissue of VILI rats, and the pathological damage degree, inflammatory reaction and apoptosis in the lung tissue of VILI rats were significantly increased; T-5224 inhibited c-Fos protein expression in lung tissues, and T-5224 inhibit the inflammatory reaction and apoptosis of lung tissue by regulating the Fas/Fasl pathway. CONCLUSIONS: c-Fos is a regulatory factor during ventilator-induced acute lung injury, and the inhibition of its expression has a protective effect. Which is associated with the antiinflammatory and antiapoptotic effects of T-5224.

[Research progress of spontaneous respiration in mechanical ventilation of acute respiratory distress syndrome].

Mechanical ventilation is an important supportive treatment for acute respiratory distress syndrome (ARDS). However, improper mechanical ventilation can cause a "second hit" to the lung, that is, ventilator-induced lung injury (VILI), characterized by translocation of pulmonary inflammatory mediators into the bloodstream, aggravating systemic inflammatory response syndrome, and multiple organ failure. Although the current protective mechanical ventilation strategy plays an important role in supporting treatment, the mortality of ARDS with mechanical ventilation is still very high. Therefore, to explore the strategy of pulmonary protective ventilation has always been the key orientation of ARDS and has important clinical significance. This article reviews the application, advantages and disadvantages of assisted and non-assisted spontaneous respiration in ARDS patients undergoing mechanical ventilation, in order to provide a reference for research and development of new strategies for ARDS protective ventilation.

Epidemiology of metabolic syndrome and its components in Chinese patients with a range of thyroid-stimulating hormone concentrations.

OBJECTIVE: To investigate the relationship between thyroid stimulating hormone (TSH) concentration and the risks of developing metabolic syndrome and its components. METHODS: A total of 10,140 residents of the Yunyan district of Guiyang (Guizhou, China) who were ≥40 years old were selected by cluster random sampling between May and August 2011, of whom 5692 were eligible. TSH concentration and indices of metabolic syndrome were documented at baseline and 3 years later. Participants were allocated to a euthyroid (TSH 0.55-4.78 mIU/L) or high TSH concentration (TSH >4.78 mIU/L) group. Patients with overt hypothyroidism or were undergoing treatment for hypothyroidism were excluded. RESULTS: The crude and adjusted prevalences of metabolic syndrome were 39.9% and 33.9% in the euthyroid group and 44.3% and 37.5% in the high TSH group, respectively. Binary logistic regression analysis revealed a positive correlation between a high TSH concentration at baseline and the cumulative incidence of metabolic syndrome during follow up. CONCLUSIONS: High TSH is associated with a higher risk of developing metabolic syndrome or one of its components; therefore, people with a high TSH concentration should be screened regularly to permit the early identification of metabolic syndrome and followed up thoroughly.