HBx가 간섬유화에 미치는 영향과 해마의 간 보호 효과

Abstract

Hepatitis B virus infection causes liver fibrosis which leads to cirrhosis and hepatocellular carcinoma. However, the mechanism remains poorly understood. In this study, we found that exogenous Hepatitis B virus X protein (HBx) increased fibrotic markers (vimentin and fibronectin) in Huh7 cells, suggesting that HBx induced fibrosis. To examine whether HBx regulates hepatic fibrosis through Epithelial-to-mesenchymal transition (EMT), we validated the expression of EMT regulator, snail and slug. Slug mRNA and protein levels were significantly increased by HBx transfection. On the other hand, snail protein showed no significant increase while HBx transfection increased snail mRNA significantly. Thus, HBx-induced EMT is regulated by slug rather than snail. Oxidative stress caused by NADPH oxidase (NOX) system in liver has been reported to play a critical role in several liver disease and hepatic fibrosis. The mRNA and protein level of NOX4 was increased by HBx transfection. Since NOX4-induced reactive oxygen species may increase slug and snail, HBx may be a key mediator of hepatic fibrosis development via NOX4 induction. Recently, liver disease contributes to high percentage of the morbidity and mortality rates worldwide. Excessive intake of alcohol is one of the major causes of liver injury. When liver injury repeats and becomes chronic, it leads to development of fibrosis and cirrhosis. In the liver, TGF-β is a profibrogenic cytokine, which participates in various critical events causing liver fibrosis. Seahorse (Hippocampus abdominalis) has been widely used for centuries as a common traditional Chinese medicine. Seahorse is known to have a variety of bioactivities, such as antioxidant, anti-fatigue, and anti-tumor. Peptide is one of the main compounds of a seahorse. In this study, we isolated enzymatic hydrolysate from seahorse H. abdominalis by alcalase hydrolysis and investigated the effect of the hydrolysate on liver injury. In the present in vitro studies, the hydrolysate increases cell viability of Chang cells and protects Huh7 cells from ethanol toxicity. In addition, the hydrolysate inhibits TGF-β-induced responses. In vivo studies show that the pretreatment of hydrolysate reduces alcohol-induced increases of serum Glutamic oxaloacetic acid transaminase and Glutamic pyruvate transaminase activities and increases liver weight and body weight. These results suggest that seahorse may have a hepatoprotective effect.