Leptin reduces ventilator-induced lung injury in rats by regulating NLRP3, NLRC4 and NLRC3.

Abstract

Leptin has been linked to acute lung injury (ALI) through its regulation of immune responses. We aimed to scrutinize the effects of leptin on nucleotide oligomerization domain-like receptors containing pyrin domain 3 (NLRP3), nucleotide oligomerization domain-like receptors with caspase activation and recruitment domain 4 (NLRC4), and nucleotide oligomerization domain-like receptors with caspase activation and recruitment domain 3 (NLRC3), as an essential part of the immune system, in ventilator-induced lung injury (VILI) of rats. In the present study, pathogen-free adult male SD rats were given saline or leptin, followed by ventilation. Lung tissue samples, bronchoalveolar lavage fluids (BALF), and blood were collected four hours after installation. Notable acute lung inflammation induced by mechanical ventilation is well-characterized by a massive increase in lung injury score and wet/dry weight (W/D) ratio. We also observed VILI was associated with interleukin (IL-1β and IL-18). Rats that received ventilation showed a decrease in the levels of NLRP3 and NLRC4, and an increased level of NLRC3. Pre-treatment with leptin could abolish all of these effects induced by VILI. It has been suggested that the regulation of NLRP3, NLRC4, and NLRC3 may underlie the protection observed during VILI by exogenous leptin.