Ketamine reduces lipopolysaccharide-induced high-mobility group box-1 through heme oxygenase-1 and nuclear factor erythroid 2-related factor 2/ p38 mitogen-activated protein kinase.

摘要: Abstract Background Ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist, is widely used as an intravenous anesthetic agent and has also been shown to possess anti-inflammatory effects, but its effects on high-mobility group box-1(HMGB1) have not well defined. In the present study, we investigated of ketamine HMGB1 in lipopolysaccharide (LPS)-induced Raw264.7 cells mouse model cecal ligation puncture-induced sepsis. Materials methods were incubated with or without 1 μg/mL LPS presence absence ketamine, mitogen-activated protein kinases (MAPKs) inhibitor, small interfering RNA (siRNA). The expression levels inflammatory mediators, such HMGB1, nitric oxide (NO), heme oxygenase-1(HO-1), measured using enzyme-linked immunosorbent assays, Western blot analysis, real-time polymerase chain reaction. effect nuclear factor erythroid 2-related 2 (Nrf2) MAPKs activation was evaluated assays analysis. Results In vitro , inhibits NO release induces HO-1 concentration-dependent manner, whereas siRNA antagonizes inhibition NO. inhibited by p38 MAPK inhibitor SB203580 Nrf2 siRNA, indicating that via Nrf2. In vivo increases survival decreases serum lung Conclusions Ketamine LPS-induced through induction, these may be mediated blockade signaling pathways.