Effects of high-tidal-volume mechanical ventilation on the expression of P₂X₇ receptor and inflammatory response in lung tissue of rats

Abstract

Ventilator-induced lung injury is a severe complication mainly caused from mechanical ventilation (MV), associated with the upregulation of inflammation response. The mechanism still remains unclear. This study aims to explore the effects of pathological damage, neutrophil infiltration, expression of P 2 X 7 receptor, and activation of Caspase-1 in lung tissue using a rat model. Sprague Dawley (SD) rats were randomly divided into sham group, conventional MV group, and high-tidalvolume ventilation group and fed with clean water and rat food. The sham group received tracheotomy without MV; conventional MV group was given 7 mL/kg tidal volume ventilation, and high-tidal-volume MV group was given 28 mL/kg tidal volume ventilation. All the rats were sacrificed after 4 h of ventilation or spontaneous breath. Lung wet/dry ratio was measured, and paraffin sections were prepared for pathological injury assessment and immunohistochemistry of P 2 X 7 and myeloperoxidase levels. Lung homogenate was used for Western blot analysis of P 2 X 7 receptor and Caspase-1 levels and real-time polymerase chain reaction (PCR) analysis of P 2 X 7 gene expression level. Compared to sham group and conventional MV group, high-tidal-volume MV led to an increase in lung wet/dry ratio and histology score. High-tidalvolume ventilation also led to chemotaxis of neutrophils. The expression levels of protein and messenger RNA (mRNA) of P 2 X 7 receptor were significantly upregulated. Cleaved-caspase-1 expression was also upregulated. All data provide the evidence that high-tidal-volume MV can lead to lung injury, neutrophils infiltration, and upregulation of cleaved-Caspase-1 level. This result may be related to the upregulation of P 2 X 7 receptor expression.