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 in vivo 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 in vitro 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.
Highlights
Renal ischemia/reperfusion is an important cause of death worldwide
NR8383 rat alveolar macrophages were treated with serum from a rat model of renal ischemia/reperfusion (rI/R), with or without propofol treatment
With the respective doses of propofol, P10 levels were reduced to 2.8- and 1.6-fold of control levels, apoptosis-associated specklike protein containing a CARD (ASC) levels were reduced to 2.4- and 1.3-fold of control levels, and nucleotide oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) levels were reduced to 2.7- and 1.7-fold of control levels (P
Summary
Renal ischemia/reperfusion (rI/R) is an important cause of death worldwide. The risk of mortality due to rI/R is two to three times higher for those with acute lung injury (ALI) [1,2,3], so it is crucial to determine ways of inhibiting this complication. Treatments regulating blood glucose concentrations, blood pressure and oxidative stress have not been found to reduce deaths associated with rI/R-induced ALI [4, 5]. Augmented serum concentrations of inflammatory factors have been recognized as strong predictors of rI/R risk and ALI development [6]. NLRP3 suppresses sirtuin 1 (SIRT1), a recognized inhibitor of alveolar macrophage injury [11, 12]; restoring SIRT1 levels could be a promising way to ameliorate NLRP3 inflammasome-induced alveolar macrophage activation. There is clear evidence that inhibiting the NLRP3 inflammasome reduces inflammatory responses [13], and NLRP3 inflammasome antagonists have mostly been successful in treating rI/R [14,15,16], but their effects on rI/R-induced ALI have not been reported
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
