高迁移率族蛋白1在呼吸机相关性肺损伤大鼠中的表达变化

Study on the Expression of High Mobility Group Box-1 Protein in Rat Model of Ventilator-Induced Lung Injury

目的:探讨呼吸机相关性肺损伤(ventilator-induced lung injury,VILI)大鼠肺组织中高迁移率族蛋白1(high mobility group box 1,HMGB1)的表达变化。方法:将24只成年SD大鼠随机分为3组,每组8只。对照组:自主呼吸;大潮气量组:潮气量(TV)=30 mL/kg;丙酮酸乙酯(ethyl pyruvate,EP)干预组:尾静脉注射EP(100 mg/kg),机械通气模式同大潮气量组。采用Western blotting、RT-PCR、ELISA检测大鼠血清、肺泡灌洗液、肺组织以及牵张24 h后肺泡巨噬细胞的培养液中的HMGB1以及炎性因子的水平。结果:大潮气量组大鼠血清、肺泡灌洗液及肺组织中HMGB1含量较对照组增加。体外肺泡巨噬细胞培养液中的HMGB1在机械牵张的作用下也呈现上升趋势。EP干预后,VILI大鼠肺组织中HMGB1减少,且细胞凋亡信号通路相关蛋白Caspase3、Caspase9和聚腺苷二磷酸核糖聚合酶(PARP)表达增加。结论:VILI大鼠模型中HMGB1的表达增加,可能与肺泡巨噬细胞受机械牵张有关;EP干预对VILI肺组织有一定保护作用。

Objective：To investigate the expression of high mobility group box-1（HMGB1）in rat model of ventilator-induced lung injury（VILI）.Methods：Twenty-four healthy adult SD rats were randomly divided into three groups,with8 rats in each group.The control group：autonomous respiration.The large tidal volume group：tidal volume（TV）=30 mL/kg.The ethyl pyruvate（EP）intervention group：EP 100 mg/kg via the caudal vein and the same ventilation mode as the large tidal volume group.The levels of HMGB1 and inflammatory factors in serum and bronchoalveolar lavage fluid（BALF）and lung tissues,as well as in the culture medium of alveolar macrophages before and after mechanical stretching,were detected with Western blotting,RT-PCR and ELISA.Results：The levels of HMGB1 in serum,BALF and lung tissues of the large tidal volume group were higher than those of the control group.HMGB1 in the culture medium of alveolar macrophages was increased under mechanical stretching.The expression of HMGB1 decreased,and the proteins related to signal pathway of apoptosis as Caspase3,Caspase9 and PARP increased,in lung tissues of rat with VILI after EP intervention.Conclusions：The expression of HMGB1 increases in rat model of VILI,which may be related with the effect of mechanical stretching on alveolar macrophages.EP intervention had certain protective effect on lung tissues with VILI.