Peroxiredoxin 6 knockout aggravates cecal ligation and puncture-induced acute lung injury

Background: The aim of present study was to investigate the effects and mechanisms of peroxiredoxin (Prdx) 6 on cecal ligation and puncture (CLP) induced acute lung injury (ALI) in mice. Methods: The cecal of male Prdx 6 knockout and wildtype C57BL/6J mice were ligated and perforated. Stool was extruded to ensure wound patency. Two hours, 4 h, 8 h and 16 h after stimulation, the morphology, wet/dry ratio, protein concentration in bronchial alveolar lavage fluid (BALF) were measured to evaluate lung injury. Myeloperoxidase (MPO) activity, hydrogen peroxide (H2O2), malondialdehyde (MDA), total superoxide dismutase (SOD), xanthine oxidase (XOD), CuZn-SOD, total anti-oxidative capability (TAOC), glutathione peroxidase (GSH-PX), catalase (CAT) in lungs were measured by assay kits. The mRNA expression of lung tumor necrosis factor (TNF-alpha), interleukin (IL)-1 beta, and matrix metalloproteinases (MMP) 2 and 9 were tested by realtime RT-PCR. The nuclear factor (NF)-kappa B activity was measured by TransAM kit. Results: CLP-induced ALI was characterized by inflammation in morphology, increased wet/dry ratio, elevated protein concentration in BALF and higher level of MPO activity. The levels of H2O2, MDA, and XOD were significantly increased and SOD, CuZn-SOD, GSH-PX, CAT, and T-AOC were significantly decreased in lungs after CLP. The activity of NF-kappa B was significantly increased and subsequently, the mRNA expression of TNF-alpha, IL-1 beta and MMP2 and MMP9 were significantly increased after CLP. Those above injury parameters were more severe in Prdx 6 knockout mice than those in wildtype mice. Conclusions: Prdx 6 knockout aggravated the CLP induced lung injury by augmenting oxidative stress, inflammation and matrix degradation partially through NF-kappa B pathway.