Changes Of Inflammatory Mediators And Protective Effects Of N-acetylcysteine And Dexamethasone On Ventilator-induced Lung Injury In An Rat Model

OBJECTIVE Purpose of the present Study was to explore changes of inflammatory mediators and protective effects of N-acetylcysteine and dexamethasone to ventilator-induced lung injuy in an rat model.METHODS We established a rat model of acute lung injury by mechanical ventilation with a large vital tidal of 40ml/Kg. After anesthesia was administered and tracheotomy was performed, 40 healthy male Sprague-Dawley rats were randomly divided into four groups to receive two ventilation protocols for 4 hrs: group A was severd as control groups (n=l0,V_T-8ml/Kg), group B received large tidal volume ventilation (n=10,V_T=40mL/Kg), group C(n=10)and D(n=10) received the same tidal volume as group B with pre-treatment of N-acetylcysteine and dexamethasone separately Artriai blood gases were measured every one hour After 4 hrs, a final right lung bronchoalveolar lavage was performed. The concentrations of total protein in bronchoalveolar lavage fluid (BALF), Wet to dry right lung weigh ratio (W/D), TNF-α, IL-1β levels in BALF and serum, MDA, SOD levels in lung and serum were assayed respectively Total White blood cells (WBC) and neutrophils in BALF were counted and lung histopathology were assessed among four groups.RESULTS After 4 hrs mechanicl ventilation, arterial oxygen pressrue (PaO₂) was significantly lower in group B than in group A, C and D. A large guantity of WBCs and neutrophils infiltration were found in BALF of group B, While the amount of WBCs and neutrophils were decreased in group C and D than group B. Proinflammatory cytokines such as THF-α, IL-1β levels in BALF and in serum were significantly increased in group B than in group A, while decreased in group C and D than in group B. Malondialdehyde (MDA) were produced profoundly in the lungs and blood of group B, while decreased in group C and D than in grouP B, but the Ievels of suPeroxide dismutaSe(SOD)in the ltmgs and blood were sighficanly lower in grouP B than in grOuP A,While increased in grOuP C and D than in grouP B. The total protein contentsin BALF wer significantiy higher in grouP B than in grouP A, Whiledecreased in grOuP C and D than in grouP B. Wto of right lung weresighficanly higher in grouP B than in grouP A, While decreased in grouP Cand D than in grouP B. HiStoPathologic findings demonStrated moreinfiltraing neutrophils, deStrUCtive change of the alveolar Wall in grouP Bthan other grouPs.CONCLUSIONS These resIJlts suggeSt tha a series of proiallaxnmatoryiallanunatOry reactions and the imbalanced oxidativendioxidative reactionmay be involved in the course of veniIator-indued ltmg injuy.N-acetylcystCine and dexamethasone haV obvious protective effects onWlator-induced lung injuy in an rat model through theiranti - infl anunati on/an ox idat potCnts. Thes e re sult s al s o sugg e st tha largetidal volume can affeCt the release of cytokines into systeInic circulation, afinding tha may have relevance for development of systendc edanunatoryresPonse (Soo or multisystem ogu failure peSOF).