High-mobility group box 1 protein is involved in the protective effect of Saquinavir on ventilation-induced lung injury in mice

Saquinavir （SQV） is the first FDA approved HIV protease inhibitor. Previous studies showed that SQV can limit Toll-like receptor-4 （TLR4）-mediated inflammatory pathway and nuclear factor-κB （NF-κB） activation, thereby playing a protective role in many kinds of diseases. High-mobility group box 1 （HMGB1） has been identified as an inflammatory mediator and it might express its toxicity in a short period of time in ventilator-induced lung injury （VILI）. In this study, C57BL/6 mice were randomly divided into four groups （n = 10）： control group and control with SQV group （Con ＋ SQV） were spon- taneous breath. HTV group （HTV） received high tidal volume ventilation （HTV） for 4 h. HTV with SQV group （HTV ＋ SQV） were pretreated with 5 mg/kg of SQV for 7 days before HTV. Mice were sacrificed after 4 h of HTV. Lung wet/dry weight （W/D） ratio, alveolar-capillary permeability to Evans blue albumin （EBA）, cell counts, total proteins in bronchoalveolar lavage fluid （BALF）, tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） level in BALF and lung tissue, and lung histopathology were examined. Our results showed that HTV caused significant lung injury and NF-κB activation, which was correlated with the increase of TNF-α and IL-6 levels in BALF and plasma. SQV pretreatment significantly attenuated pulmonary inflammatory injury, as well as NF-κB activation. These findings indicate that the protective effect of SQV may be associated with the inhibition of NF-κB activation and HMGB1 expression in mice.