Pneumonia is a major cause of morbidity and mortality of
infectious diseases, especially in children.
Ripasudil (K-115), a selective ROCK inhibitor, is a promising emerging
drug against
glaucoma, and reported to have anti-inflammatory activity. However, the anti-inflammatory effect of
ripasudil still remains unclear in
pneumonia. The goal of this study is to investigate the role and the underlying mechanism of
ripasudil in
pneumonia. BALB/c mice were used to establish an acute
pneumonia model of mice by injection of
lipopolysaccharide (LPS) intraperitoneally.
Ripasudil (0.5 mg, 1 mg, 2 mg) was administrated 1 h before the induction of LPS. The histoligical change of lung tissue was evaluated by
hematoxylin-
eosin staining and
lung wet/dry ratio. Inflammatory
cytokines secretion,
oxidant-
antioxidant factors levels were measured. Cell apoptosis was examined using TNUEL assay. Western blot and qRT-PCR was used to determine gene expressions. Results showed that
ripasudil significantly attenuated LPS-induced histological changes, reduced the production of pro-inflammatory
cytokines, and alleviated LPS-induced oxidative stress in mice. LPS-induced cell apoptosis and associated
protein expression changes were attenuated by
ripasudil. Besides,
ripasudil reduced the expression of RhoA, and decreased the activity of RhoA/ROCK signaling. Finally, the level of RhoA and eNOS from
pneumonia patients exhibited negatively correlated, whereas the level of RhoA was higher while eNOS level was lower than that in the healthy control. The results of the present study indicate that
ripasudil attenuate LPS-induced
pneumonia in BALB/c mice by ameliorating
inflammation, oxidative stress and apoptosis through inhibiting RhoA/ROCK signaling pathway.
Ripasudil might be a novel and effective
drug for the treatment of
pneumonia.