Anti-inflammatory effect of tranexamic acid against trauma-hemorrhagic shock-induced acute lung injury in rats.

It has been demonstrated that tranexamic acid (TXA), a synthetic derivative of lysine, alleviates lung damage in a trauma-hemorrhagic shock (T/HS) model. Nevertheless, the mechanism of TXA against acute lung injury (ALI) has not deeply elaborated. In this study, we generated a T/HS rat model based on previous research, and TXA (50 mg/kg and 100 mg/kg) was intravenously injected into these rats prior to or post T/HS. The results revealed that the decreased survival rate and impaired lung permeability of the rats caused by T/HS were improved by TXA pretreatment or posttreatment. T/HS-triggered over-generation of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in bronchoalveolar fluid and serum was inhibited by TXA, and the enzymatic activity of myeloperoxidase (MPO) in lung tissues was suppressed by TXA as well. Furthermore, TXA treatment deactivated the poly ADP-ribose polymerase-1 (PARP1)/nuclear factor kappa B (NF-kappa B) signaling pathway in the lungs of T/HS rats, as evidenced by increased I kappa B alpha expression, and decreased cleaved PARP1, p-p65 (Ser276), p-p65 (Ser529), p-I kappa B alpha (ser32/ser36), and intercellular adhesion molecule-1. While the expression level of total p65 did not change after T/HS, its DNA binding activity was strengthened. Both TXA pretreatment and posttreatment suppressed this effect on the DNA binding activity of NF-kappa B. Taken together, our results reveal that administration of TXA effectively relieves T/HS-induced ALI, at least in part, by attenuating the abnormal pulmonary inflammation.