Abstract
Objective It has been reported that the intravenous anesthetic propofol (PPF) has anti-inflammatory effects in vitro and in patients. The purpose of this study was to investigate whether PPF has anti-inflammatory effects in lipopolysaccharide (LPS)-induced septic shock by inhibiting the induction of pro-inflammatory cytokines [inter-leukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] and high mobility group box 1 (HMGB1) in rats. Methods Thirty six male Wistar rats were randomly assigned to one of three groups (control group, PPF + LPS group and LPS group; n = 12 per group). Control group rats received a 0.9% NaCl solution (NS) by the tail vein. The PPF + LPS group rats received PPF (10 mg/kg bolus, followed by infusion at 10 mg/(kg · h) through a femoral vein catheter) 1 h before LPS (7.5 mg/kg) administration via the tail vein. The LPS group rats received injection of LPS (7.5 mg/kg) via the tail vein. Hemodynamic effects were recorded as well as mortality rates, and plasma cytokine con-centrations (TNF-α, IL-6, HMGB1) were measured for the 24-h observation period. Results The mean arterial pressure and heart rate of the PPF + LPS group were more stable than those of the LPS group. The mortality at 24 h after the administration of the LPS injection was much higher in the LPS group (58.3%) compared to the PPF + LPS group (25.0%). Plasma concentrations of cytokines (IL-6 and TNF-α) and HMGB1 were significantly reduced in the PPF + LPS group compared to the LPS group ( P < 0.05). Conclusion Pretreatment with PPF reduced the mortality rate of rats and attenuated the pro-inflammatory cytokine responses in an endotoxin shock model through an anti-inflammatory action inhibiting induction of HMGB1.
Highlights
Sepsis and septic shock are common problems in the intensive care unit and carry a very high mortality rate
An endotoxin injection reduced mean arterial pressure (MAP) in both the LPS group and PPF+LPS group, while MAP remained unchanged in the control group
There were no significant differences in heart rates (HR) among the groups for the first 6 h of the experiment (Fig. 1)
Summary
Sepsis and septic shock are common problems in the intensive care unit and carry a very high mortality rate. Various complications that accompany sepsis, such as disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS), are refractory to therapy, even with current advanced therapeutic methods. Sepsis is potentially fatal if not treated appropriately[1,2], and many clinical therapies, It has been demonstrated that high mobility group box 1 (HMGB1) protein is an important late-phase mediator in the pathogenesis of sepsis[5]. HMGB1 is a non-histone nuclear protein originally identified as an important factor in the regulation of genetic informa-. Wang et al found that HMGB1 could be actively released from necrotic or damaged cells, or secreted by activated monocytes/ macrophages. The release of HMGB1 into the extracellular space is controlled by pro-inflammatory cytokines[8]
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