Abstract:
Objective:To investigate the effects of fasudil on the acute lung injury(ALI) in rats induced by lipopolysaccharide(LPS) through the RhoA/Rho kinase pathway.Methods:Eighteen wistar rats were randomly divided into control group,LPS group and fasudil(FAS) group(6 rats each group).The ALI model was established by intraperitoneal injection of LPS 1 mg/kg for 16 hours,and then endotracheal instillation of LPS 3 mg/kg.The fasudil 10 mg/kg was intraperitoneally injected into FAS group at 30 min before intraperitoneal injection of LPS and 1 hour after endotracheal instillation of LPS.The rats were sacrificed after 3 hours.The morphological changes of lung tissue in 3 groups were observed by HE staining,the ratio of wet-to-dry weight of lung,myeloperoxidase activity,malondialdehyde content in 3 groups were measured,and the ROCK2(Rho kinase 2) mRNA and protein expressions in 3 groups were detected by reverse transcription-polymerase chain reaction and Western blot,respectively.Results:Compared with the control group,the lung histopathology change in LPS group was obvious,and the lung histopathology change in FAS group was significantly gentler than that in LPS group.The ratio of wet-to-dry weight of lung,myeloperoxidase activity,malondialdehyde content in LPS group were significantly higher than those in control group(P0.01),but the indexes in FAS and LPS group were decreased to varying degrees(P0.05 to P0.01).Compared with the control group,the ROCK2 mRNA expression of lung in LPS group was increased(P0.01),but the difference of which had no statistical significance between FAS and LPS group(P0.05).Compared with the control group,the ROCK2 protein expression in LPS group was significantly increased(P0.01).Compared with the LPS group,the ROCK2 protein expression in FAS group was significantly decreased(P0.05).Conclusions:Fasudil can reduce the acute lung injury in rats induced by lipopolysaccharide through the RhoA/Rho kinase signal pathway.