地塞米松调节claudin-4减轻海水淹溺性肺水肿的机制研究

目的探讨地塞米松对海水淹溺性肺水肿的保护作用及其分子机制。方法采用气管内滴注海水的方法复制海水淹溺性肺损伤的大鼠模型,测定肺水肿的指标及肺组织中claudin-4、核转录因子-κB(NF-κB)、p38蛋白水平的表达;培养A549细胞,分别应用NF-κB抑制剂、p38抑制剂、糖皮质激素受体(GR)阻断剂(RU486)研究地塞米松改善海水淹溺性肺水肿的分子机制。结果吸入海水后肺水肿形成,海水可活化NF-κB及p38,同时下调claudin-4,地塞米松可缓解上述改变;应用PDC抑制NF-κB活化,并采用SB203580抑制p38活化可缓解海水诱导的claudin-4下调和单层细胞通透性的增高,应用RU486阻断GR后,地塞米松上调claudin-4的作用则大大降低。结论地塞米松可抑制海水诱导的NF-κB活化,缓解NF-κB活化介导的claudin-4表达下调及肺通透性增高,从而减轻海水淹溺性肺水肿。

Dexamethasone attenuates seawater drowning-induced pulmonary edema by up-regulating claudin-4

Objective To confirm the protective effects of dexamethasone against seawater drowning- induced pulmonary edema （ SWD-PE ） , and investigate the underlying mechanisms both in vivo and in vitro. Methods SWD-PE model was built by endotraeheal instillation of seawater; pulmonary edema indexes were estimated and the expression of claudin-4, NF-κB and p38 were evaluated by Western Blot; the mechanisms of dexamethasone improving seawater inhalation induced pulmonary edema were also studied using A549 cell line intervened with NF-κB, p38 and glucocorticoid receptor （GR） inhibitors. Results Seawater inhalation could result in lung edema, activate NF-κB and p38, and deregulate the expression of claudin-4 while dexamethasone alleviated lung pulmonary edema. The inhabitation of NF-κB and p38 with PDC and SB203580 respectively could reverse the suppression of claudin-4 and the increasing of monolayer cell permeability resulted from seawater stimulation. Conclusion Dexamethasone attenuated seawater drowning induced lung edema by suppressing NF-κB activation, up regulating claudin-4 expression and reducing the pulmonary permeability.