Liu Su, Feng Guang, Wang Guang-Lei, Liu Gong-Jian
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, People's Republic of China.
Eur J Pharmacol. 2008 Apr 14;584(1):159-65. doi: 10.1016/j.ejphar.2008.02.009. Epub 2008 Feb 14.
The pathogenesis of acute lung injury/acute respiratory distress syndrome (ARDS) is complex and involves multiple signal transduction processes. It is believed that p38MAPK (mitogen-activated protein kinase) is one of the most kinases in inflammatory signaling. At present study, we demonstrated the role of p38MAPK in lipopolysaccharide (LPS)-induced acute lung injury with pharmacologic p38MAPK inhibition by SB203580. SB203580, p38MAPK specific inhibitor, was injected (10 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). The hematoxylin-eosin staining of lung tissues showed that p38MAPK inhibition significantly attenuated the pulmonary inflammatory responses induced by LPS. Moreover, SB203580 can also inhibit the inflammatory cytokine release, and reduce the mortality rate of LPS-induced acute lung injury. Further, western blot analysis that showed SB203580 administration can inhibit the activation of NF-kappaB, which was associated with the inhibition of IkappaBalpha degradation in cytoplasm. These data suggest that p38MAPK signaling may be involved in the activation of NF-kappaB, and activation of p38MAPK signaling may be one of the mechanisms of acute lung injury.
急性肺损伤/急性呼吸窘迫综合征（ARDS）的发病机制复杂，涉及多个信号转导过程。据信，p38丝裂原活化蛋白激酶（p38MAPK）是炎症信号传导中最重要的激酶之一。在本研究中，我们通过使用SB203580对p38MAPK进行药理学抑制，证明了p38MAPK在脂多糖（LPS）诱导的急性肺损伤中的作用。在给予LPS（5 mg/kg，静脉注射）前30分钟，注射p38MAPK特异性抑制剂SB203580（10 mg/kg，静脉注射）。肺组织苏木精-伊红染色显示，抑制p38MAPK可显著减轻LPS诱导的肺部炎症反应。此外，SB203580还可抑制炎症细胞因子的释放，并降低LPS诱导的急性肺损伤的死亡率。进一步的蛋白质印迹分析表明，给予SB203580可抑制核因子κB（NF-κB）的激活，这与抑制细胞质中IκBα的降解有关。这些数据表明，p38MAPK信号通路可能参与NF-κB的激活，p38MAPK信号通路的激活可能是急性肺损伤的机制之一。
