| Objective Peroxisome proliferator-activated receptor (PPARs) are a class of ligand activated nuclear transcription factor, is divided into PPARα, PPARβand PPARγsubtypes. WY14643 is a synthetic PPAR-αagonist,which has a large expression of lung tissue.There are many studies indicate that WY14643 has the effects of lipid-lowering, hypoglycemic, anti-inflammatory and antioxidant in recent years. Different doses of WY14643 protect against lipopolysaccharide (LPS) induced acute lung injury, but different doses of WY14643 on ventilator-induced lung injury has not been reported.The purpose of this study is to explore the different doses of WY14643 on ventilator-induced lung injury and its possible mechanism.Methods Male Sprague-Dawley rats (weighing 250 to 300g)were used in these experiments. The high tidal volume (VT40ml/kg) mechanical ventilation were given to set up ventilator-induced lung injury model. Rats were randomly divided into four experimental groups each containing eight rats. C group: control group, no mechanical ventilation; V group: model group, after tracheostomy tube, the rats were received high tidal volume mechanical ventilation (40ml/kg);W1 and W2 group: WY14643-1mg/kg and WY14643-3mg/kg group, animals were pretreated with Wy14643 at the dose of 1, 3mg/kg 1h before ventilation. The rats were sacrificed by exsanguination at the end of 2h mechanical ventilation, bronchoalveolar lavage fluid(BALF),lung tissue and arterial blood were collected.The measured indexes include: the levels of MDA,SOD in the blood plasma,MIP-2 and TNF-αin bronchoalveolar lavage fluid (BALF),Arterial blood gases were measured at 0h,1h,2h of ventilation,PaO2 were record to calculate the oxygenation index, Wet-to-dry weight ratio(W/D)of lung were assayed respectively. Lung pathological change was observed by microscope. the expression of NF-κB in the lung was determined by immunohistochemical method. Finally, data were expressed as mean±SD. The statistical significance of differences between groups were analyzed using the oneway analysis of variance (ANOVA) and methods of LSD with the SPSS13.0 for windows XP statistical software package. Statistical differences were considered significant if the P value was < 0.05.Result With the mechanical ventilation time lasting , compared with C group ,the oxygenation index of group V,W1 and W2 were significantly lower(P<0.05).Compared with V group, W1 and W2 group were markedly increased the oxygenation index(P<0.05). Compared with W1 group, W2 group was significantly increased the oxygenation index(P<0.05). Compared with C group, the lung tissue from the V group was markedly damaged characterized by alveolar wall thickening,rupture, alveolar fused into a sheet, the alveolar wall and pulmonary interstitium were full of inflammatory cell, with diffusing congestion,edema and hemorrhage,necrosis.W1 group with a little thickening of lung alveolar wall and interstitium, few infiltration of inflammatory cells and red blood cell. The W2 group only a few inflammatory cell infiltration. The V,W1 and W2 group significantly decreased serum SOD activity and increased serum MDA concentration, W/D lung weight ratio and TNF-αand MIP-2 concentrations in BALF as compared with group C( P<0.05 ) .Wy14643 pretreatment significantly attenuated these mechanical ventilation-induced changes in group W1 and W2 in a dose-dependent manne(rP<0.05). Compared with C group, the expression of NF-κB of group V,W1 and W2 were significantly increased(P<0.05).Compared with V group, W1 and W2 group were markedly decreased the expression of NF-κB(P<0.05). Compared with W1 group, W2 group was significantly decreased the expression of NF-κB(P<0.05).Conclusion Injection of Wy14643 by intravenous 1h before ventilation exert significant dose dependent protection against from the rat lung VILI, whose mechanism may be associated with repression of inflammatory factors and attenuation of oxidative stress reaction.
|
PDF Full Text Request