Ma Hui-Jie, Huang Xin-Li, Liu Yan, Fan Ya-Min
Department of Physiology, Hebei Medical University, Shijiazhuang 050017, China.
Acta Pharmacol Sin. 2012 Aug;33(8):983-90. doi: 10.1038/aps.2012.70. Epub 2012 Jul 16.
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.
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.
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.
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.
我们推测多形核中性粒细胞（PMN）凋亡增强可能是肺部PMN浸润受到抑制的原因。本研究旨在探讨二氧化硫（SO₂）对体内外PMN凋亡的影响，这可能介导SO₂对肺部疾病的保护作用。
通过气管内注入脂多糖（LPS，100μg/100g，溶于200μL生理盐水）诱导成年雄性SD大鼠急性肺损伤（ALI）。在LPS处理前30分钟腹腔注射SO₂溶液（25μmol/kg）。LPS处理6小时后处死大鼠。收集肺组织进行组织病理学研究和SO₂浓度测定。收集支气管肺泡灌洗液（BALF）用于PMN凋亡检测。体外实验中，培养大鼠外周血PMN，并用LPS（30mg/L）和SO₂（10、20和30μmol/L）处理6小时，通过蛋白质印迹法检测凋亡相关蛋白表达，用流式细胞术测量凋亡率。
与对照组相比，LPS处理显著降低了肺组织和外周血中的SO₂浓度。SO₂预处理可防止LPS诱导的肺组织和外周血中SO₂浓度降低。LPS处理显著降低了体内外PMN凋亡，而SO₂预处理可防止这种降低。与单独给予LPS相比，SO₂预处理使Caspase-3和Bax的蛋白水平显著升高，但Bcl-2水平降低。
SO₂在LPS诱导的ALI过程中作为PMN凋亡的调节剂发挥重要作用，这可能是SO₂对肺部疾病保护作用的潜在机制之一。
