The Effect And Mechanisem Of ROCK Inhibitor On Sepsis Liver Injury

Objective: To investigate the effect and mechanism of ROCK inhibitor Y-27632 in sepsis liver injury.Methods: The model was obtained by CLP method,Thirty-two adult male SD rats were randomly divided into the following groups: sham operation group（Sham group）,sham operation+Y-27632（5mg/kg）group（Sham+Y group）,cecal ligation and perforation group（CLP group）and CLP+Y group-27632 group（CLP+Y group）,each of group has 8 animals.Blood was collected from the heart and the rats were euthanized 24 h after surgery,and the serum and liver tissue were collected for further study.Hematoxylin-eosin staining（HE）was used to observe the histopathological changes in the livers of the rats in each group;enzyme-linked immunosorbent assay（ELISA）: serum samples and liver tissue homogenates from different groups were taken to observe the alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,interleukin 18（IL-18）,interleukin 10（IL-10）and glutathione（GSH）levels;Western blotting（Western Blot）was used to detect the changes of ROCK1 protein in rat liver tissue.Results:1.HE results: The liver tissue structure in the Sham group was normal,the liver cells were not deformed or destroyed,and the liver boundary plate was intact;compared with the Sham group,there was no significant change in the Sham+Y group.The hepatocytes in the CLP group were irregular in shape,disordered in arrangement and structure,necrotic hepatocytes were vacuolated and balloon-like,and a large number of inflammatory cells were infiltrated around the central vein.The pathological morphology of hepatocytes in the CLP+Y group was significantly improved compared with the CLP group.2.Liver function indicators and GSH: ALT and AST in CLP group were significantly higher than those in Sham group after 24 hours;ALT and AST in CLP+Y group were significantly lower than those in CLP group（P<0.05）.3.ELISA results: Compared with the Sham group,the levels of IL-18 in the liver tissue homogenate in the CLP group increased（P<0.05）,while the levels of IL-10 and GSH decreased（P<0.05）;Compared with CLP+Y group,the level of IL-18 decreased（P<0.05）,and the levels of IL-10 and GSH increased（P<0.05）.4.Western Blot:Compared with the Sham group,the expression of ROCK1 protein in the CLP and CLP+Y groups was increased（P<0.05）;compared with the CLP group,the ROCK1 protein expression in the CLP+Y group was decreased（P<0.05）.Conclusion:Pretreatment with ROCK inhibitor Y-27632 can alleviate liver injury in septic rats,and the mechanism may be related to inhibiting Rho/ROCK signaling pathway and its downstream inflammatory factors,reducing inflammatory response in liver tissue and reducing the level of oxidative stress in liver.