APOCYNIN ATTENUATES LIPOPOLYSACCHARIDE-INDUCED LUNG INJURY IN AN ISOLATED AND PERFUSED RAT LUNG MODEL

作者：Chian Chih Feng; Chiang Chi Huei^*; Chu Yuan Jung; Chuang Chiao Hui; Liu Shiou Ling; Jheng Yi Han; Zhang Haibo; Rya Jay H

来源：Shock, 2012, 38(2): 196-202.

DOI：10.1097/SHK.0b013e31825a1982

• Apocynin
• LPS
• ARDS
• inflammation
• NADPH
• MAPK
• NF-kappa B

Apocynin (Apo) suppresses the generation of reactive oxygen species that are implicated in lipopolysaccharide (LPS)-induced lung injury (LPSLI). We thus hypothesized that Apo may attenuate LPSLI. In addition, we explored the cellular and molecular mechanisms of Apo treatment in LPSLI. Lipopolysaccharide-induced lung injury was induced by intratracheal instillation of 10 mg/kg LPS in isolated and perfused rat lung model. Apocynin was administered in the perfusate at 15 min before LPS was administered. Hemodynamics, lung injury indices, inflammatory responses, and activation of apoptotic pathways were assessed. There was an increase in lung vascular permeability associated with lung weight gain after LPS exposure. The levels of interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), macrophage inflammatory protein 2, H2O2, and albumin increased in the bronchoalveolar lavage fluid. Adhesion molecule of neutrophil (CD31) was upregulated. The expression of TNF-alpha, IL-1 beta, glutathione, myeloperoxidase, JNK, P38, caspase 3, p-AKT, and plasminogen activator inhibitor 1 in lung tissue was greater in the LPS groups when compared with the control group. Upregulation and activation of nuclear factor kappa B occurred along with increased histopathologic lung injury score in LPSLI. The Apo attenuated these inflammatory responses including the levels of CD31, H2O2, TNF-alpha, IL-1 beta, myeloperoxidase, P38, and nuclear factor kappa B along with downregulation of apoptosis as reflected by caspase 3 and p-AKT. In addition, Apo attenuated the increase in lung weight, bronchoalveolar lavage fluid albumin content, and the histopathologic lung injury score. In conclusion, LPSLI is associated with increased inflammatory responses, apoptosis, and coagulation. The administration of Apo attenuates LPSLI through downregulation of the inflammatory responses and apoptosis.

• 出版日期2012-8