Effects of serum of rats with ventilator-induced lung injury on endothelial cell permeability and its mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of inflammatory mediators in the serum of rats with ventilator-induced lung injury (VILI) on endothelial cellular cytoskeleton and monolayer cellular permeability and explore the molecular mechanism of VILI-induced lung edema.</p><p><b>METHODS</b>Thirty healthy male SD rats were divided into 3 groups, namely group A with normal tidal volume ventilation, group B with high tidal volume ventilation and group C with high tidal volume ventilation plus ulinastatin treatment. The serum was collected from each rat after ventilation and added into endothelial cell line ECV-304 culture medium, and 2 h later the changes of F-actin and cell permeability were observed.</p><p><b>RESULTS</b>Compared to sera from rats with normal tidal volume ventilation, the sera of rats with high tidal volume ventilation caused obvious reorganization of actin cytoskeleton with weakened fluorescent intensity at the peripheral filament bands and formation of long and thick stress fibers in the center, which resulted in endothelial contraction and increased cell permeability. Pretreatment with ulinastatin could lessen these changes significantly. The percentage in change of permeability coefficient (Ppa%) after stimulation with the sera of rats in groups A, B and C was (6.95+/-1.66)%, (27.50+/-7.77)%, and (17.71+/-4.66)%, respectively, showing statistically significant differences (P<0.05).</p><p><b>CONCLUSION</b>The pro-inflammatory mediators in the serum of rats with high tidal volume ventilation increases endothelial cell permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin can lessen the hyperpermeability by inhibiting multiple pro-inflammatory mediators.</p>

Effects of serum of the rats ventilated with high tidal volume on endothelial cell permeability and therapeutic effects of ulinastatin / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>With the widespread use of ventilators in treating critically ill patients, the morbidity of ventilator-induced lung injury (VILI) is increasing accordingly. VILI is characterized by a considerable increase in microvascular leakiness and activation of inflammatory processes. In this study we investigated the effects of inflammatory mediators in VILI rat serum on endothelial cytoskeleton and monolayer cellular permeability, as well as the therapeutic effect of ulinastatin, to explore the pathogenesis and the relationship between biotrauma and lung oedema induced by VILI.</p><p><b>METHODS</b>Thirty healthy male Sprague-Dawley rats were randomly divided into three groups: group A (normal tidal volume ventilation), group B (high tidal volume ventilation) and group C (high tidal volume ventilation plus ulinastatin). The serum of each rat after ventilation was added to endothelial cell line ECV-304 medium for two hours to observe the effects of serum and/or ulinastatin on endothelial fibrous actin and permeability.</p><p><b>RESULTS</b>Compared to rats ventilated with normal tidal volume, serum of rats ventilated with high tidal volume caused a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity at the peripheral filament bands and formation of the long and thick stress fibres in the centre resulting in endothelial contraction and higher permeability. Prior treatment with ulinastatin lessened the above changes significantly. The changes of permeability coefficient of endothelial permeability after group A, B or C rats serum stimulation were (6.95 +/- 1.66)%, (27.50 +/- 7.77)% and (17.71 +/- 4.66)% respectively with statistically significant differences (P < 0.05) among the three groups.</p><p><b>CONCLUSIONS</b>The proinflammatory mediators in the serum of the rats given high tidal volume ventilation increases endothelial permeability by reorganizing actin cytoskeleton, and pretreatment with ulinastatin lessens the permeability by inhibiting of proinflammatory mediators.</p>