Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6254234 | Journal of Surgical Research | 2014 | 12 Pages |
Backgroundischemic preconditioning (IPC) protects against liver ischemia-reperfusion (IR) injury. The mechanism involves nitric oxide metabolism but the importance of endothelial nitric oxide synthase (eNOS) has not been established. Heme oxygenase-1 (HO-1) protects against liver IR but it is unclear if this depends on nitric oxide synthase.Materials and methodsA mouse model of IPC with liver IR using wild-type (WT) and eNOS transgenic knockout (eNOSâ/â) mice was developed to study the role of eNOS and its relationship to HO-1. Serum alanine aminotransferase level, liver histopathologic injury scores, and liver microcirculatory blood flow were measured. Western blots measured liver HO-1/2, eNOS, phosphorylated eNOS, inducible nitric oxide synthase, and reverse transcription-polymerase chain reaction (HO-1). A set of 24-h recovery experiments was undertaken on WT mice with measurement of serum alanine aminotransferase level, histologic injury score, and HO-1 by Western blot.ResultsIn WT animals, IPC preceding IR resulted in a reduction in hepatocellular and histologic injury, and improvement in parenchymal perfusion. In contrast, IPC in the eNOSâ/â model did not protect the animals from IR injury. There was no difference between the eNOS and phosphorylated eNOS expression in all the WT groups. HO-1 protein was not detected in the nonrecovery groups but HO-1 messenger RNA was detected in all groups. In WT recovery experiments, IPC was protective against IR injury. HO-1 protein was detected in the IPCÂ +Â IR and IR only groups but not in the sham group.ConclusionsThis study developed and used an eNOSâ/â model to demonstrate that eNOS mediates protection against liver IR injury by IPC. The eNOS expression and activity and HO-1 expression are increased independently in liver IPC and IR, with HO-1 expression increased in the later stages of IPC and IR.