Research Paper Volume 13, Issue 1 pp 865—876
Propofol reduces renal ischemia/reperfusion-induced acute lung injury by stimulating sirtuin 1 and inhibiting pyroptosis
- 1 Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, Hebei, China
- 2 Department of Gastroenterology, Cangzhou Central Hospital, Cangzhou, Hebei, China
- 3 Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, Hebei, China
Received: July 9, 2020 Accepted: September 21, 2020 Published: December 1, 2020
https://doi.org/10.18632/aging.202191How to Cite
Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Abbreviations
ALI: acute lung injury; ASC: apoptosis-associated speck-like protein containing a CARD; SIRT1: sirtuin 1; IL-18: interleukin 18; IL-1β: interleukin 1β; NLRP3: nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3; rI/R: renal ischemia/reperfusion; TBST: Tris-buffered saline and Tween 20.