Expression and role of inducible nitric oxide synthase in ischemia-reperfusion liver in rats.

OBJECTIVE: To investigate the expression and the role of iNOS expression in hepatic ischemia-reperfusion (I/R) injury. METHODS: Male Wistar rats were subjected to 30-minute hepatic ischemia, then iNOS protein and iNOS mRNA expression in liver tissue was assessed by Western blot and RT-PCR analysis respectively at different time points after reperfusion. The effects of L-NAME (Nomega-nitro-L-arginine methyl ester, a nonselective NOS inhibitor) or AE-ITU (aminoethytl-isothiourea, a relative selective inhibitor of iNOS) treatment were also evaluated. RESULTS: High levels of iNOS protein and mRNA expression were detected in the liver tissue subjected to I/R, but not in the sham-operated rats. iNOS protein and iNOS mRNA expression reached a maximum on the first day after reperfusion and decreased later. The levels of iNOS protein and iNOS mRNA disappeared on 7th, 3rd day after reperfusion respectively. The high iNOS expression was correlated with hepatic dysfunction. L-NAME administration worsened hepatic dysfunction induced by hepatic I/R. In contrast, AE-ITU administration showed mild protective effects against hepatic dysfunction induced by hepatic I/R. CONCLUSION: Ischemia-reperfusion may induce or up-regulate the expression of iNOS protein and iNOS mRNA, which is detrimental to hepatic I/R injury