woLiver Regeneration Effect of Oncostatin M Following Hepatectomy for the Rat Cirrhotic Liver Model

摘要

Background/Aims: Liver resection represents the treatment of choice for hepatocellular carcinoma (HCC) arising in well-compensated cirrhosis. Gene expression of the multifunctional cytokine, Oncostatin M (OSM), stimulates liver regeneration and adenoviral vector expressing OSM (AdOSM) allows a persistent expression of the gene. The aim of this study is to evaluate the benefits of the preoperative injection of AdOSM to the remnant lobes to regenerate the liver. Methods: A 70% partial hepatectomy was performed in dimethylnitrosamine-administrated cirrhotic rats with a preoperative injection of AdOSM, adenoviral vector carrying β-galactosidase (AdLacZ), or phosphate-buffered saline (PBS). The morphologic, histologic, and biochemical changes in the remnant liver and survival rates were then assessed. Results: Portal injection with clamping the portal branches of the resected lobes for 5 min made it possible to effectively transduce the adenoviral vector into the remnant lobes. The ratio of the remnant liver weight/body weight (%) was 2.3 ± 0.5 in the AdOSM group, 1.1 ± 0.3 in the AdLacZ group (p < 0.001), and 1.6 ± 0.4 in the PBS group (p = 0.02). The fibrous ratio (%) was 21.3 ± 4.6 in the AdOSM group and 35.2 ± 4.5 in the AdLacZ group on day 4 after hepatectomy and fibrous status was significantly decreased in the AdOSM group (p = 0.02). Serum hyaluronic acid which is the indicator of liver fibrosis was 215 ± 141 ng/mL in the AdOSM group and 1963 ± 1225 ng/mL in the AdLacZ group (p = 0.03). Conclusions: The OSM gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration.