Inhibition of c-Jun N-terminal Kinase Signaling Pathway Alleviates Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Rats.

Background: An acute respiratory distress syndrome (ARDS) is still one of the major challenges in critically ill patients. This study aimed to investigate the effect of inhibiting c-Jun N-terminal kinase (INK) on ARDS in a lipopolysaccharide (LPS)-induced ARDS rat model. Methods: Thirty-six rats were randomized into three groups: control, LPS, and LPS + INK inhibitor. Rats were sacrificed 8 h after LPS treatment. The lung edema was observed by measuring the wet-to-dry weight (W/D) ratio of the lung. The severity of pulmonary inflammation was observed by measuring myeloperoxidase (MPO) activity of lung tissue. Moreover, the neutrophils in bronchoalveolar lavage fluid (BALF) were counted to observe the airway inflammation. In addition, lung collagen accumulation was quantified by Sircol Collagen Assay. At the same time, the pulmonary histologic examination was performed, and lung injury score was achieved in all three groups. Results: MPO activity in lung tissue was found increased in rats treated with LPS comparing with that in control (1.26 +/- 0.15 U in LPS vs. 0.77 +/- 0.27 U in control, P < 0.05). Inhibiting INK attenuated LPS-induced MPO activity upregulation (0.52 +/- 0.12 U in LPS + INK inhibitor vs. 1.26 +/- 0.15 U in LPS, P < 0.05). Neutrophils in BALF were also found to be increased with LPS treatment, and inhibiting INK attenuated LPS-induced neutrophils increase in BALF (255.0 +/- 164.4 in LPS vs. 53 (44.5-103) in control vs. 127.0 +/- 44.3 in LPS + JNK inhibitor, P < 0.05). At the same time, the lung injury score showed a reduction in LPS + JNK inhibitor group comparing with that in LPS group (13.42 +/- 4.82 vs. 7.00 +/- 1.83, P = 0.001). However, the lung W/D ratio and the collagen in BALF did not show any differences between LPS and LPS + INK inhibitor group. Conclusions: Inhibiting INK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.