Mechanistic study of the protective effects of propofol on a rat model of ventilator-induced lung injury

Objective To investigate the role of p38 MAPK pathway in propofol-induced inhibition of high mobility group box 1(HMGB1) expression in lung tissue in a rat model of ventilator-induced lung injury.Methods Thirty-two healthy Sprague Dawley(SD) rats were randomly divided into 4 groups(n=8 each):group A,spontaneous breathing;group B,small tidal volume ventilation(VT=8 ml /kg),group C,high tidal volume ventilation(VT=30 ml /kg) and group D,high tidal volume ventilation(VT=30 ml /kg) with intravenous administration of propofol 8 mg /(kg.h).The animals were mechanically ventilated for 4 h and then all animals were sacrificed.The lungs were removed for:(1) lung lavage,determination of total protein content,and WBC and neutrophil counts in broncho-alveolar lavage fluid(BALF);(2) determination of W /D lung weight ratio and myeloperoxidase(MPO) activity;(3) determination of HMGB1 protein and mRNA expression and p38 MAPK activity in lung tissue.Results The inflammatory response,as evidenced by total protein(1.58 ±0.46)g /L and WBC(112.05 ±21.33) × 10 7 /L in BALF,W /D lung weight ratio(8.25±0.92) and MPO activity(3.08±0.85)U /g were significantly higher in group C compared with group A(P0.05);The expressions of HMGB1 protein(0.43±0.13) and mRNA(0.30±0.08),and p38 activity(0.52±0.11) were also significantly increased in group C(P0.05).The above indexes in group D were significantly lower than the group C(P0.05).Conclusion Propofol attenuated high tidal volume ventilation-induced acute lung injury,which may be related to the downregulation of HMGB1 protein and mRNA expression through p38 MAPK signal pathway.