Therapeutic effects of simvastatin combined with kallistatin treatment for pediatric burn patients with sepsis

摘要

The aim of the present study was to examine the combined efficacy of simvastatin and kallistatin treatment for pediatric burn sepsis. A total of 72 pediatric patients with burn sepsis were recruited and randomly divided into 3 groups, receiving simvastatin (40 mg/day), kallistatin (20 mg/day) or combined treatment. ELISA, reverse transcription-quantitative polymerase chain reaction, western blotting and flow cytometry were used to analyze the therapeutic effects of simvastatin and kallistatin. The results revealed that combined treatment in pediatric burn sepsis patients decreased the inflammatory cytokine tumor necrosis factor α and interleukin (IL)-1β serum levels, whereas it increased IL-10 and human leukocyte antigen-D related levels. In addition, administration of combined simvastatin and kallistatin decreased the blood urea nitrogen and serum creatinine levels in the patients. It was also demonstrated that Toll-like receptor 4 expression on the surface of monocytes was markedly decreased, while suppressor of cytokine signaling-3 expression was increased in the combined treatment group as compared with the kallistatin or simvastatin treatment alone. Combined treatment also promoted human endothelial cell (HEC) growth compared with the single treatment groups and inhibited the high mobility group box-1 (HMGB1) levels, HMGB1-induced nuclear factor-κB activation and inflammatory gene expression levels in these cells. The study further demonstrated that combined treatment significantly decreased HEC apoptosis through the upregulation of B-cell lymphoma 2 (Bcl-2) and P53 expression levels, as well as downregulation of Bcl-2-associated X protein and caspase-3 levels. In conclusion, these observations indicated that combined treatment with simvastatin and kallistatin inhibited HEC apoptosis, which may be a potential therapeutic strategy for the treatment of pediatric burn sepsis patients.