Propofol ameliorates endotoxin‑induced myocardial cell injury by inhibiting inflammation and apoptosis via the PPARγ/HMGB1/NLRP3 axis.

Abstract

Endotoxin lipopolysaccharide (LPS) is one of the primary causes of myocardial injury. Propofol confers protective effects against LPS-induced myocardial damage; however, the biological functions and mechanisms underlying propofol are not completely understood. The present study aimed to investigate the effects of propofol on LPS-induced myocardial injury. Primary neonatal rat cardiomyocytes were treated with LPS to establish a myocardial injury model. LDH release in the culture media was measured using a LDH assay kit. The interactions between NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing A CARD (ASC) and pro-caspase-1 were determined using a co-immunoprecipitation assay. Cell viability was measured using an MTT assay, and the levels of cell apoptosis were determined using flow cytometry, JC-1 staining (mitochondrial membrane potential) and caspase-3 activity assays. The mRNA expression levels of TNF-α, IL-6, IL-1β and IL-18, and the protein expression levels of NLRP3, ASC, pro-caspase-1, caspase-1 p10, pro-IL-1β, IL-1β, pro-IL-18, IL-18, high mobility group box-1 (HMGB1) and peroxisome proliferator-activated receptor γ (PPARγ) were analyzed using reverse transcription-quantitative PCR and western blotting analyses, respectively. ELISAs were performed to measure the production of inflammatory mediators, including TNF-α, IL-6, IL-1β and IL-18. The present results demonstrated that pretreatment with propofol significantly attenuated LPS-induced neonatal rat cardiomyocyte injury in a concentration- and time-dependent manner. Propofol pretreatment also significantly inhibited LPS-induced cardiomyocyte inflammation and apoptosis. The results suggested that propofol pretreatment inactivated HMGB1-dependent NLRP3 inflammasome signaling, which involved PPARγ activation. Therefore, the results indicated that propofol reduced endotoxin-induced cardiomyocyte injury by inhibiting inflammation and apoptosis via the PPARγ/HMGB1/NLRP3 axis, suggesting that propofol may serve as a potential therapeutic agent for septic myocardial damage.