Role of NLRP3 inflammasome in the obesity paradox of rats with ventilator-induced lung injury

The objective of this research is to determine the action of the nucleotide oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome in the obesity paradox of rats with ventilator-induced lung injury (VILI). Twenty-four (average weight: 250 ± 20 g) pathogen-free adult male Sprague Dawley (SD) rats were randomly classified as group A and group B, while twelve obese (420 ± 20 g) pathogen-free adult male SD rats were classified as group C. Three groups received open tracheotomies after anesthesia. Group A then underwent spontaneous breathing for 4 h after endotracheal intubation, and group B and group C were then connected to a ventilator to administer high tidal volume ventilation (V_T=30 mL/kg) for 4 h; All groups then underwent open tracheotomy. Blood, bronchoalveolar lavage fluid (BALF), and lung tissue were obtained for related testing at the end of ventilation. The lung injury score, the wet/dry weight (W/D) ratio, inflammatory content, and cytokine level in BALF and serum were lower for group C than for group B. For instance, compared with group B, the level of PaO₂ in serum separated from blood was higher than in group C, while the lungs of group B were highly enriched with NLRP3, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and cysteinyl aspartate specific proteinase 1 (caspase-1). Causal mechanisms for the obesity paradox in VILI might partly be related to the NLRP3 inflammasome.

Keywords: NLRP3 inflammasome; inflammation; obesity paradox; ventilator-induced lung injury.