罗格列酮对小鼠机械通气相关性肺损伤的影响
Effects of rosiglitazone on ventilator-associated lung injury in mice
目的 评价罗格列酮对小鼠机械通气相关性肺损伤(VALI)的影响.方法 健康雄性C57小鼠24只,体重20~25 g,6~8周龄,采用随机数字表法分为3组(n=8),假手术组(S组)仅行气管切开;VALI组行机械通气,通气频率80次/min,持续时间4h,VT40 ml/kg,FiO221%,I:E=1:2,PEEP 0;罗格列酮组(RGZ组):机械通气前30 min口服罗格列酮30 mg/kg,其余处理同VALI组.通气结束后处死小鼠,行左侧支气管肺泡灌洗,对支气管肺泡灌洗液(BALF)行中性粒细胞计数,取右肺上叶组织行HE染色,光镜下观察,行肺损伤评分;采用ELISA法测定右肺中叶组织IL-1β、TNF-α、高迁移率族蛋白1(HMGB1)及晚期糖基化终末产物受体(RAGE)的含量.结果 与S组比较,VALI组BALF中性粒细胞计数、肺组织IL-1β、TNF-α、HMGB1、RAGE含量及肺损伤评分升高(P<0.01),RGZ组上述指标差异无统计学意义(P>0.05).与VALI组比较,RGZ组BALF中性粒细胞计数和肺组织IL-1β、TNF-α、HMGB1、RAGE含量及肺损伤评分降低(P<0.01).结论 罗格列酮可减轻小鼠VALI.
更多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-lbeta (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<0.01),and no significant change was found in the parameters mentioned above in group RGZ (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.
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