01 May 2019 : Animal Research
Propofol Protects Lung Endothelial Barrier Function by Suppression of High-Mobility Group Box 1 (HMGB1) Release and Mitochondrial Oxidative Damage Catalyzed by HMGB1Zhou Feng1AB, Jian-Wei Wang1CD, Yan Wang2F, Wen-Wen Dong2EG*, Zi-Feng Xu1AE
Med Sci Monit 2019; 25:3199-3211
BACKGROUND: The processes of mechanical ventilation-induced lung injury (VILI) triggers the release of high-mobility group box 1 (HMGB1), a prominent damage-associated molecular pattern (DAMP) family member, which can cause damage to pulmonary vascular endothelial cells. We aimed to determine whether propofol protected against endothelial cell injury induced by HMGB1 in vitro and in vivo.
MATERIAL AND METHODS: ICR mice (male) were mechanically ventilated for 4 h after anesthetization at both low tidal volume (LVT, 6 ml/kg) and high tidal volume (HVT, 30 ml/kg). A propofol bolus (10 mg/kg) was administered to the animals prior to the onset of ventilation, followed by infusion at 5 mg/(kg·h). We obtained confluent cultures of mouse lung vascular endothelial cells (MLVECs) and then performed cyclic stretching at 20% stretch for 4 h with or without propofol.
RESULTS: HMGB1 reduced the expression of tight junctions between endothelial cells, including VE-cadherin and ZO-1, and increased endothelial permeability, and both were blocked by propofol. We found that MLVECs exhibited mitochondrial oxidative damage by HMGB1, which was successfully suppressed through administration of MnTBAP as well as propofol. Propofol ameliorated HVT-associated lung vascular hyperpermeability and HMGB1 production in vivo. Propofol also inhibited HMBG1 release caused by cyclic stretching in MLVECs in vitro.
CONCLUSIONS: Our results prove that the cyto-protective function of propofol protects against lung ventilation-induced dysfunction of the lung endothelial barrier. This function of propofol is mediated through inhibition of HMGB1 release caused by mechanical stretching and mitochondrial oxidative damage triggered by HMGB1.
Keywords: acute lung injury, HMGB1 Protein, Mitochondria, Propofol, Stress, Mechanical, Catalysis, endothelial cells, Endothelium, Vascular, Lung, Mice, Inbred ICR, RNA, Recombinant Proteins, Respiration, Artificial, Tidal Volume, ventilator-induced lung injury
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