Respiratory Department, Peking University Third Hospital, Beijing 100191, China.
Cytokine. 2011 Mar;53(3):334-41. doi: 10.1016/j.cyto.2010.12.006. Epub 2010 Dec 28.
Hydrogen sulfide (H₂S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H₂S may be a crucial mediator in airway responsiveness and airway inflammation in a rat model of chronic exposure to cigarette smoke (CS). Rats randomly divided into control and CS-exposed groups were treated with or without sodium hydrosulfide (NaHS, donor of H₂S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H₂S-synthesizing enzyme) for 4-month exposure. Serum H₂S level and CSE protein expression in lung tissue were higher, by 2.04- and 2.33-fold, respectively, in CS-exposed rats than in controls (P<0.05). Exogenous administration of NaHS to CS-exposed rats alleviated airway reactivity induced by acetylcholine (Ach) or potassium chloride (KCl) by 17.4% and 13.8%, respectively, decreased lung pathology score by 32.7%, inhibited IL-8 and TNF- α concentrations in lung tissue by 34.2% and 31.4%, respectively, as compared with CS-exposed rats (all P<0.05). However, blocking endogenous CSE with PPG in CS-exposed rats increased airway reactivity induced by Ach or KCl, by 24.1% and 24.5%, respectively, and aggravated lung pathology score, by 44.8%, as compared with CS-exposed rats (all P<0.01). Incubation in vitro with NaHS, 1-3 mmol/L, relaxed rat tracheal smooth muscle precontracted by Ach or KCl. However, the NaHS-induced relaxation was not blocked by glibenclamide (10⁻⁴ mol/L), L-NAME (10⁻⁴ mol/L), or ODQ (1 μmol/L) or denudation of epithelium. Endogenous H₂S may have a protective role of anti-inflammation and bronchodilation in chronic CS-induced pulmonary injury.
硫化氢（H₂S），最近被认为是第三种内源性气态递质，在全身炎症中可能具有重要作用。我们研究了内源性 H₂S 是否可能是慢性暴露于香烟烟雾（CS）的大鼠模型中气道反应性和气道炎症的关键介质。大鼠随机分为对照组和 CS 暴露组，分别用或不用硫氢化钠（NaHS，H₂S 的供体）或炔丙基甘氨酸（PPG，胱硫醚-γ-裂解酶[CSE]的抑制剂，一种 H₂S 合成酶）处理 4 个月。CS 暴露组大鼠血清 H₂S 水平和肺组织中 CSE 蛋白表达分别升高 2.04 倍和 2.33 倍（均 P<0.05）。CS 暴露大鼠给予外源性 NaHS 可分别使乙酰胆碱（Ach）或氯化钾（KCl）诱导的气道反应性降低 17.4%和 13.8%，使肺病理评分降低 32.7%，使肺组织中 IL-8 和 TNF-α浓度分别降低 34.2%和 31.4%，与 CS 暴露大鼠相比（均 P<0.05）。然而，用 PPG 阻断 CS 暴露大鼠内源性 CSE 可使 Ach 或 KCl 诱导的气道反应性分别增加 24.1%和 24.5%，并使肺病理评分增加 44.8%，与 CS 暴露大鼠相比（均 P<0.01）。1-3 mmol/L 的 NaHS 孵育可使 Ach 或 KCl 预收缩的大鼠气管平滑肌松弛。然而，Glibenclamide（10⁻⁴ mol/L）、L-NAME（10⁻⁴ mol/L）或 ODQ（1 μmol/L）或去上皮不能阻断 NaHS 诱导的松弛。内源性 H₂S 可能在慢性 CS 诱导的肺损伤中具有抗炎和支气管扩张的保护作用。
