The Therapeutic Effects Of Augmenter Of Liver Regeneration On Rat Liver Fibrosis And Its Mechanism

Liver fibrosis is a common pathological process of chronic hepatic disease, which can lead to cirrhosis and increase risk for hepatocellular carcinoma. In China, liver fibrosis and cirrhosis are usually caused by the developing of chronic viral hepatitis. Here we evaluated the therapeutic efficacy of augmenter of liver regeneration (ALR) on liver fibrosis induced by carbon tetrachloride (CC14) and porcine-serum (PS), and investigated potential mechanisms.Accumulated studies had revealed that ALR appeared to be an important regulator of liver regeneration and had trophic effects on damaged liver in animal models of acute or chronic liver injury. In these studies, exogenous ALR administration ameliorated hepatic damage, enhanced hepatic proliferative capacity post-toxininduced liver injury, or improved survival of toxin-administered animals. The present research was to observe the therapeutic effects of ALR on liver fibrosis and to explore the molecular mechanism of antifibrosis.ALR might attenuate liver injury and fibrosis by suppressing oxidative stress, down-regulating profibrogenic factors, and blocking HSCs activation. This report demonstrated that ALR therapy diminished α-smooth muscle actin (SMA) expression, decreased intrahepatic reactive oxygen species (ROS) level, and down-regulated transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, and tissue inhibitor of metalloproteinase (TIMP)-1expression. Compared with the model rats, cirrhotic rats treated with ALR showed ameliorated biochemical liver tests. In these animals, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (AKP) were significantly lower and serum albumin (ALB) significantly higher than in cirrhotic rats and similar to healthy controls. These favorable changes were accompanied by histological improvement with marked reduction of fibrosis and decreased expression of collagen I and IV in ALR-treated rats. Compared with cirrhotic rats, ALR treatment were able to reduce the level of malondialdehyde (MDA) content, increased superoxide dismutase (SOD) activity. Compared healthy control rats, the Hyp content of cirrhotic rats was significantly increased, however, the Hyp content was marked reduced in ALR-treated rats, compared with cirrhotic rats. In conclusion, these results provided novel insights into the mechanisms of ALR in the protection of the liver.