Protection of ripasudil, a Rho kinase inhibitor, in lipopolysaccharides-induced acute pneumonia in mice.

Protection of ripasudil, a Rho kinase inhibitor, in lipopolysaccharides-induced acute pneumonia in mice. Am J Transl Res. 2019;11(10):6433-6443 Authors: He P, Guo Y, Wang J, Yan L, Feng A Abstract 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, ripas...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research