Effects of Growth Hormone on Hepatic Tissue Regeneration after a Partial Hepatectomy in Rat

Rhee, Joong Eui; Suh, Gil Joon; Kim, Young Deok; Jung, Sung Eun; Youn, Yeo Kyu

Abstract

BACKGROUND: The regeneration mechanisms of liver tissue after liver injury or a partial hepatectomy are clinically and experimentally a very important medical issue. There have been some reports that hepatic tissue regeneration after liver injury or a partial hepatectomy is started and stopped by signals between the parenchymal cells and non-parenchymal cells of the liver, and that nitric oxide (NO) and TNF-alpha mediate those interactions. Several ex vivo studies have shown the function of NO in liver regeneration, but few in vivo studies have been reported. We tried to prove the regeneration stimulating effect of growth hormone and to define the function of nitric oxide and TNF-alpha in the early stage of liver regeneration by using in vivo methods.
METHODS
Sprague-dawley rats with a body weight of about 300 gm were used and they were devided into a control group and two experimental groups: a partial hepatectomy (PH)-only group and a partial hepatectomy with growth hormone (GH) injected group. In the experimental groups, about 70-75% of liver tissue was resected under general anesthesia. Ten rats from each subgroup were sacrificed at 6 hours, 12 hours and 24 hours after PH respectively, and blood samples and remaining liver tissue were taken. The TNF-alpha level in serum, the MDA (malondialdehyde) activity, the SOD (superoxide dismutase) activity, and the i-NOS activity in hepatic tissue, as well as DNA synthesis rate of regenerating liver cells, were measured.
RESULTS
The DNA synthesis rate of liver tissue was stationary until 12 hours after PH but was abruptly increased at 24 hours after PH. By GH injection, this increment of DNA synthesis rate was doubled. i-NOS activity of liver tissue was increased as much as 3 times than that of control group by 6 hours after PH, and more increased by 24 hours after PH. With injection of GH, this increment of i-NOS activity was significantly potentiated. The serum TNF-alpha level was abruptly increased 6 times more than that of control group by 6 hours after PH, then showed decreasing tendency by 24 hours after PH. With the injection of GH, this increment of TNF-alpha level after PH was significantly suppressed. The MDA level in liver tissue was significantly increased at early stage of regeneration and gradually more increased until 24 hours after PH. But the SOD activity was slightly exhausted after PH. The GH injection after PH showed a remarkable antioxidant effect.
CONCLUSIONS
The administration of GH after PH had a definitely potentiating effect of hepatocyte regeneration, and the effect seemed to be mediated by nitric oxide. It was strongly suggested that NO synthesis at early stage of liver regeneration after PH was an important step to induce the initiation of liver cell proliferation.