Effects of Rho kinase inhibitors on septic liver injury
10.12092/j.issn.1009-2501.2022.05.007
- Author:
Bomin XING
1
;
Na GUO
1
;
Haihui NING
1
;
Xinyun DING
1
;
Yuqing MA
2
Author Information
1. The First Clinical Medical College of Lanzhou University
2. Department of Anesthesiology, the First Hospital of Lanzhou University
- Publication Type:Journal Article
- Keywords:
Liver injury;
ROCK1 protein;
Sepsis;
Y-27632
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2022;27(5):544-550
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effect of Rho kinase inhibitor Y-27632 on acute liver injury in sepsis. METHODS: Thirty-two healthy adult male SD rats were randomly divided into sham operation group (Sham group), sham operation+Y-27632 group (Sham+Y group), cecal ligation and perforation group (CLP group) and CLP+Y-27632 group (CLP+Y-27632 group), 8 animals in each group. The rat sepsis model was established by the CLP method, and the rat was euthanized 24 hours after the model was established, and the serum and liver tissue were collected. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the liver tissue of the rats in each group; Western Blot was used to detect the expressions of ROCK1 and downstream NF-κB proteins in the liver tissue of the rats in each group; immunohistochemical method The expression of ROCK1 protein in liver tissue of rats was detected; enzyme-linked immunosorbent assay (ELISA) method was used to detect the levels of serum liver function indexes ALT and AST, and the changes of IL-18, IL-10 and GSH contents in liver tissue homogenate. RESULTS: Compared with the Sham group, there was no significant change in the histopathology of the liver in the Sham+Y group. In the CLP group, the arrangement of hepatocytes was disordered, with a large number of inflammatory cells infiltrating. 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). Compared with the Sham group, the expression of NF-κB protein in the CLP and CLP+Y groups increased (P<0.05); compared with the CLP group, the NF-κB protein expression in the CLP+Y group decreased (P<0.05); A small amount of expression was found in the liver Sham group, and a large amount was expressed in the CLP group and CLP+Y group; compared with the Sham group, the serum ALT and AST levels in the CLP and CLP+Y groups were increased (P<0.05). The levels of ALT and AST in +Y group decreased (P<0.05). Compared with the Sham group, the contents of IL-18 in the liver tissue homogenate of the CLP and CLP+Y groups increased (P<0.05), while the contents of IL-10 and GSH in the liver tissue homogenate of the CLP group decreased (P<0.05). The changes of IL-10 and GSH in the group were similar (P>0.05); compared with the CLP group, the content of IL-18 in the CLP+Y group was decreased (P<0.05), and the content of IL-10 and GSH was increased (P<0.05). CONCLUSION: Rho kinase inhibitor can alleviate acute liver injury in septic rats, which may be related to inhibiting the expression of ROCK1 and NF-κB proteins, reducing the inflammatory response of liver tissue, and reducing the level of liver oxidative stress.
