在歐美,造成肝纖維化主要原因為酒精性肝炎、病毒性(C型病毒)肝炎和非酒精性肝炎。相對地,在亞洲地區造成肝纖維化主要的原因為病毒性肝炎(C型病毒和B型病毒);此外,肝纖維化還會更進一步轉變成為肝硬化或肝癌。造成肝纖維化最主要的因素是因為細胞外基質的堆積而導致肝功能的缺失,在其過程中扮演最重要角色是活化態的肝星狀細胞。當肝星狀細胞由靜止態轉變成為活化態時,細胞會開始增生且造成α-SMA及膠原蛋白的大量表現。 亞洲地區,蜆被廣泛認為對於肝損傷具有保護的作用,此篇論文即是探討蜆萃取物對於肝纖維化是否具有保護療效。根據動物實驗,於大鼠灌注四氯化碳9週,再給與蜆萃取物4週,經由組織病理分析其結果顯示蜆萃取物具有修復肝臟損傷的功效。另外,細胞實驗結果顯示,蜆萃取物可以減少活化態肝星狀細胞的增生並促使細胞停滯於G1/G0期。我們亦發現蜆萃取物會減少活化態肝星狀細胞α-SMA和第一型膠原蛋白的表現,此結果顯示蜆萃取物可能具有抑制活化態肝星狀細胞的作用。
In the western world, the major causes of liver fibrosis include alcohol, chronic hepatitis C infection and NASH (non-alcoholic steatohepatitis). This contrasts with Asia and Africa where chronic viral liver disease (hepatitis B and C) causes a massive burden of liver disease and cirrhosis. Furthermore, rates of hepatocellular carcinoma are high in these areas as cirrhosis predisposes to liver cancer. Liver fibrosis is characterized by excess deposition of collagens, resulting in an impairment of liver function and finally organ failure. Liver fibrosis is characterized by an activation of hepatic stellate cells (HSC). Quiescent HSCs become an activated phenotype which is characterized by alpha-smooth muscle actin (α-SMA) upregulation, increase in cell growth, and extracellular matrix secretion. The freshwater clam (Corbicula fluminea) is a widely-consumed shellfish and is used as a remedy for liver injury and anti-alcoholic toxicity in Asia. The purpose of this study would like to determine the roles of hepatoprotective effect of clam extracts. We have set up the intragastric infusion Tsukamoto-French rat model for approach in human liver fibrosis. According to our results of in vivo experiments, the clam extracts have ability to repair the injured by carbon tetrachloride in liver. In vitro assay, clam extracts significantly decreased activated HSC proliferation and induced an increase in the number of activated HSC in the G0/G1 phase by flow cytometry. In addition, clam extracts manifestly decreased α-SMA and collagen type I expression by Western blot assay in activated HSC. These results suggest clam extracts could inhibit activation of HSC.