Propofol reduces renal ischemia/reperfusion-induced acute lung injury by stimulating sirtuin 1 and inhibiting pyroptosis

Abstract

The activation of pyroptosis is an important feature of renal ischemia/reperfusion (rI/R)-induced acute lung injury (ALI). Propofol, a general anesthetic, is known to inhibit inflammation in I/R-induced ALI. We investigated whether propofol could suppress pyroptosis during rI/R-induced ALI by upregulating sirtuin 1 (SIRT1). We generated an <i>in vivo</i> model of rI/R-induced ALI by applying microvascular clamps to the renal pedicles of rats for 45 min. Pathological studies revealed that rI/R provoked substantial lung injury and inflammatory cell infiltration. The rI/R stimulus markedly activated pyroptotic proteins such as NLRP3, ASC, caspase 1, interleukin-1β and interleukin-18 in the lungs, but reduced the mRNA and protein levels of SIRT1. Propofol treatment greatly inhibited rI/R-induced lung injury and pyroptosis, whereas it elevated SIRT1 expression. Treatment with the selective SIRT1 inhibitor nicotinamide reversed the protective effects of propofol during rI/R-induced ALI. Analogous defensive properties of propofol were detected <i>in vitro</i> in rat alveolar macrophages incubated with serum from the rI/R rat model. These findings indicate that propofol attenuates rI/R-induced ALI by suppressing pyroptosis, possibly by upregulating SIRT1 in the lungs.