Gene expression profile analysis of regenerating liver after portal vein ligation in rats by a cDNA microarray system

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Aims : We assessed changes in gene expression of hypertrophied liver after portal vein ligation (PL) in a test group of rats compared to a control group which had the same size liver but no PL.Methods : The portal veins of the left and median lobes in the test group were ligated in an initial operation. Four days after the PL, the liver volume of the posterior caudate lobe (5%) increased two-fold and comprised 10% of the liver. A 90% hepatectomy was then performed, leaving only the hypertrophied posterior caudate lobe, and leaving the normal anterior and posterior caudate lobes (10%) in the control (sham) group. A comparison of the expression profiles between two groups was performed using cDNA microarrays. And the hepatic ATP level was measured.Results : The survival rate for the PL group was significantly higher than for the sham group at 4 days after the hepatectomy (56.3% and 26.7%, p<0.05). Gene expression of cyclin D1, PCNA, cyclin A and B was up-regulated, and the CDK inhibitor was down-regulated. Increases were observed in : (i) pyruvate dehydrogenase, the TCA cycle regulator, (ii) acyl-CoA dehydrogenase, the oxidation regulator, and (iii) cytochrome oxidases, the oxidative phosphorylation regulator. Hepatic ATP concentration after hepatectomy was better maintained in the PL group than in the sham group (0.48±0.01μmol/ml vs. 0.33±0.01μmol./ml, p<0.05).Conclusion : The regenerating liver increased tolerance for extended hepatectomy compared to normal liver. It is believed that this is because the induced rapid regeneration of the remaining liver after hepatectomy increases ATP metabolism. Key words : liver regeneration, portal vein embolization, extended hepatectomy, DNA microarray, hepatic ATP level.