Objective：To investigate the protective effect of fasudil, a Rho-kinase inhibitor, on ischemia/reperfusion (I/R) injury after partial liver resection in rats and its mechanisms.
Methods：Fifty-four Wistar rats were randomly divided into group A (sham operation, control group), group B (I/R group) and group C (fasudil pretreatment + I/R group). I/R models were induced by blocking the blood supply of hepatic left lateral and median lobes (70% blood supply of liver) with an atraumatic microvascular clip for 45 min. After ischemia, the rats were reperfused and the non-ischemic hepatic lobes (30%) were resected at the same time. The serum transaminase, NO and malondialdehyde (MDA) levels, the activity of eNOS and superoxide dismutase (SOD) in liver tissues were determined at 1, 3 and 6 h after reperfusion to evaluate the hepatoprotective effects of fasudil.
Results：The liver function was improved, the SOD activity and NO level was increased, the MDA level was decreased, SOD/MDA ratio was increased and the hepatocytes impairment was alleviated significantly in group C after fasudi pretreatment. RhoA protein showed a basal expressionly in group A. RhoA protein expression significant increased in group B compared with group A, and the elevation was inhibited in group C.
Conclusions： RhoA/Rho kinase signaling pathway plays an important role in liver ischemia/reperfusion injury. Fasudil inhibits the expression of RhoA protein, regulates NO release, reduces lipid peroxidation in liver tissue and promotes clearance of free radicals. Thus, it protects the liver against 1/R injury.