BACKGROUND: To explore the protective effect of ozone-oxidative-preconditioning (OzoneOP) through the protein kinase C (PKC), ERK1/2, and heat shock protein70 (HSP70) signal transduction in rats during hepatic ischemic-reperfusion (IR) injury.
METHODS: We constructed an IR model by occluding all vessels of the rats’ left and median liver lobes for 45 min, followed by reperfusion for 3 h. Afterwards, we constructed the OzoneOP model via intraperitoneal injection of 1 mg · kg -1 · d -1 of 50 mg · L -1 ozone for 5 days to investigate the significance of PKC, ERK1/2 and HSP70 signal transduction in OzoneOP. The PKC inhibitor chelerythrine chloride (CHE), activator phorobol12-myristate13-acetate (PMA) and MEK inhibitor PD98059 were utilized to analyze the phosphorylation of PKC and the expression levels of ERK1/2 and HSP70. After ischemia and reperfusion, alanine aminotransferase (ALT) and aspartase aminotransferase (AST) were detected in the abdominal aorta blood. Meanwhile, the expression of HSP70 protein and the activities of PKC and ERK1/2 in the left hepatic lobe were analyzed, and the ultrastructure of the hepatic was observed.
RESULTS: Compared with the control group, the phosphorylation of PKC and ERK1/2 and the expression of HSP70 were higher in the OzoneOP-treated model ( P <0.05). Conversely, inhibiting PKC and ERK1/2 abolished the protection conferred by OzoneOP ( P <0.05).
CONCLUSION: OzoneOP significantly increased the expression of HSP70 by activating PKC and ERK1/2 signaling pathways, thus significantly alleviating hepatic IR injury in rats.
KEYWORDS: ERK1/2 MAPKs; HSP70; Liver ischemia-reperfusion; O zone - oxidative - preconditioning; PKC