Effects of rosiglitazone on ventilator-associated lung injury in mice

Abstract

Objective To evaluate the effects of rosiglitazone on ventilator-associated lung injury(VALI) in mice. Methods Twenty-four healthy male C57 mice, weighing 20-25 g , aged 6-8 weeks, were randomly divided into 3 groups(n=8 each)using a random number table: sham operation group(group S); group VALI; rosiglitazone group(group RGZ). The mice only underwent tracheotomy in group S. In group VALI, the mice were ventilated(respiratory rate 80 breaths/min, duration 4 h, tidal volume 40 ml/kg, fraction of inspired oxygen 21%, inspiratory/expiratory ratio 1∶2, PEEP 0). In group RGZ, 30 mg/kg rosiglitazone was given orally at 30 min before ventilation, and the other treatments were similar to those previously described in group VALI.At the end of ventilation, the mice were sacrificed, and the left lung was lavaged, and the broncho-alveolar lavage fluid(BALF)was collected for determination of neutrophil count.The pulmonary specimens were collected from the upper lobe of right lungs for microscopic examination of the pathological changes which were scored.The pulmonary specimens were obtained from the middle lobe of right lungs for measurement of the contents of interleukin-1beta(IL-1β), tumor necrosis factor-alpha(TNF-α), high mobility group box-1(HMGB-1)and receptor for advanced glycation end-products(RAGE)by enzyme-linked immunosorbent assay. Results Compared with group S, the neutrophil counts in BALF, contents of IL-1β, TNF-α, HMGB1 and RAGE, and lung injury score were significantly increased in VALI group(P 0.05). Compared with group VALI, the neutrophil counts in BALF, contents of IL-1β, TNF-α, HMGB1 and RAGE, and lung injury score were significantly decreased in group RGZ(P<0.01). Conclusion Rosiglitazone can mitigate VALI in mice. Key words: Thiazolidinediones; Respiration, artificial; Respiratory distress syndrome, adult