Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis
Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis
复制标题
二氧化硫通过增强多形核中性粒细胞凋亡减轻 LPS 诱导的急性肺损伤
DOI：
10.1038/aps.2012.70
复制
发表时间：
2012-08-01
影响因子：
8.2
通讯作者：
Fan, Ya-min
中科院分区：
文献类型：
--
作者：
Ma, Hui-jie;Huang, Xin-li;Fan, Ya-min
目的：我们推测多形核中性粒细胞(PMN)的凋亡增强可能与其抑制PMN在肺内的浸润有关。为探讨二氧化硫(SO2)在体内和体外对中性粒细胞凋亡的影响，探讨SO2对肺部疾病的保护作用。方法：成年雄性SD大鼠气管内注入脂多糖(LPS100μg/100g，含200μL生理盐水)诱导急性肺损伤(ALI)。SO2溶液(2 5μ/kg)于注射前30min腹腔注射。内毒素处理后6h处死大鼠。取肺组织进行病理组织学观察和SO2浓度测定。收集支气管肺泡灌洗液(BALF)，检测PMN凋亡率。体外培养大鼠外周血中中性粒细胞，用脂多糖(30 mg/L)和SO2(10，20，30μ/L)处理6h，用Western blotting检测细胞凋亡相关蛋白的表达，用流式细胞仪检测细胞凋亡率。结果：与对照组相比，脂多糖能显著降低肺组织和外周血中SO2的浓度。SO2预处理可预防内毒素引起的肺组织和外周血中SO2浓度的降低。与单纯给予脂多糖相比，脂多糖在体内和体外均能显著降低中性粒细胞的凋亡率，抑制中性粒细胞的凋亡。与单纯给予脂多糖相比，SO2可显著提高肺组织中Caspase-3和Bax的蛋白表达水平，降低Bc l-2的表达。结论：SO2在脂多糖诱导的ALI中起着重要的调节PMN凋亡的作用，这可能是SO2对肺部疾病保护作用的机制之一。
Aim:We speculated that the enhanced apoptosis of polymorphonuclear neutrophil (PMN) might be responsible for the inhibition of PMN infiltration in the lung. This study was designed to investigate the effects of sulfur dioxide (SO 2) on PMN apoptosis in vivo and in vitro, which may mediate the protective action of SO 2 on pulmonary diseases.Methods:Acute lung injury (ALI) was induced by intratracheally instillation of lipopolysaccharide (LPS, 100 μg/100 g, in 200 μL saline) in adult male SD rats. SO 2 solution (25 μmol/kg) was administered intraperitoneally 30 min before LPS treatment. The rats were killed 6 h after LPS treatment. Lung tissues were collected for histopathologic study and SO 2 concentration assay. Bronchoalveolar lavage fluid (BALF) was collected for the measurement of PMN apoptosis. For in vitro experiments, rat peripheral blood PMNs were cultured and treated with LPS (30 mg/L) and SO 2 (10, 20 and 30 μmol/L) for 6 h, and apoptosis-related protein expression was detected by Western blotting, and apoptosis rate was measured with flow cytometry.Results:LPS treatment significantly reduced the SO 2 concentrations in the lung tissue and peripheral blood, as compared with the control group. Pretreatment with SO 2 prevented LPS-induced reduction of the SO 2 concentration in the lung tissue and peripheral blood. LPS treatment significantly reduced PMN apoptosis both in vivo and in vitro, which could be prevented by the pretreatment with SO 2. The protein levels of Caspase-3 and Bax was significantly increased, but Bcl-2 was decreased by the pretreatment with SO 2, as compared with LPS administration alone.Conclusion:SO 2 plays an important role as the modulator of PMN apoptosis during LPS-induced ALI, which might be one of the mechanisms underlying the protective action of SO 2 on pulmonary diseases.