Propofol ameliorates endotoxin‑induced myocardial cell injury by inhibiting inflammation and apoptosis via the PPARγ/HMGB1/NLRP3 axis
- Hui Zhao
- Ying Gu
- Hai Chen
Affiliations: Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi 710032, P.R. China
- Published online on: December 30, 2020 https://doi.org/10.3892/mmr.2020.11815
Copyright: © Zhao
et al. This is an open access article distributed under the
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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.