Study on SIRT1-NLRP3 axis-mediated pyroptosis in the role of remifentanil against liver ischemia-reperfusion injury

Objective To investigate the role and mechanism of silent information regulator 1 (SIRT1)-NOD-like receptor protein 3 (NLRP3) axis in the effect of remifentanil against ischemia-reperfusion injury (IRI) in rat livers.

Methods SD rats were randomly divided into sham operation group (sham group), IRI group, IRI+remifentanil pretreatment group (IRI+RPC group), IRI+SIRT1 inhibitor EX-527 group (IRI+EX-527 group) and IRI+RPC+EX-527 group, with 8 rats in each group. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), interleukin (IL)-1β and IL-18 of rats in each group were detected. The liver tissue pathology was observed. The apoptosis rate of hepatocytes in rats was detected. The expressions of SIRT1, NLRP3, cleaved cysteinyl aspartate specific proteinase-1 (Cleaved Caspase-1) and Gasdermin D (GSDMD) proteins in rat liver tissue were detected.

Results Compared with the sham group, the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI group were increased, the serum ALT, AST, LDH, IL-1β, and IL-18 levels were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05). Compared with the IRI group, the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+RPC group were decreased, the serum ALT, AST, LDH, IL-1β, and IL-18 levels were decreased, the relative expression of SIRT1 protein in liver tissue was increased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were decreased; the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+EX-527 group were increased, the ALT, AST, LDH, IL-1β, and IL-18 levels were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05). Compared with the IRI+RPC group, the liver tissue pathological score and hepatocyte apoptosis rate in the IRI+RPC+EX-527 group were increased, the levels of ALT, AST, LDH, IL-1β, and IL-18 were increased, the relative expression of SIRT1 protein in liver tissue was decreased, and the relative expression of NLRP3, Cleaved Caspase-1, and GSDMD proteins were increased (all P<0.05).

Conclusions SIRT1 may participate in the regulation of remifentanil against rat liver IRI by inhibiting NLRP3 mediated cell pyroptosis.