Negative Regulatory Effect of Somatostatin on Experimental Rat Hepatic Fibrosis

Objective To clarify the actions of somatostatin (SST) on the hepatic fibrogenesis in experimental rats. Methods Seventy five Sprague-Dawley rats were divided into 5 groups at random, including normal control, model control, SST-treated model groups of high, medium and low doses (200 μg•kg^(-1)•d^(-1), 100 μg•kg^(-1)•d^(-1) and 50 μg•kg^(-1)•d^(-1), respectively) (n=15, in each group). All rats, except for the normal controls, were injected with 40% carbon tetrachloride (CCl4) subcutaneously for 8 weeks to establish hepatic fibrosis. Meanwhile, rats of SST-treated model groups were given different doses of SST twice a day in the same way. Then the liver function, serum levels of hyaluronic acid (HA), laminin (LM), and collagen type Ⅳ (CⅥ) were tested. The collagen types Ⅰ and Ⅲ, and pathological changes in liver tissue were assessed. Results Being compared with the model control group, SST-treated groups, especially the medium and low dose ones, exhibited significantly improved indices of liver function, including alanine minotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TBJL) and alkaline phosphatase (ALP). Markedly lowered expression of serum HA, LM and tissular collagen types Ⅰ, Ⅲ were also detected radioimmunologically and immunohistochemically in the low dose SST-treated model group. Moreover, pathological findings, such as lessened fibrous septa, decreased hepatic stellate cells (HSCs), alleviated hepatic steatosis and attenuated inflammation, confirmed the significant improvement in fibrotic degree under the treatment of low dose rather than other doses of SST. Conclusion SST exerts the negative modulatory effect on hepatic fibrosis with a pathophysiological basis of extra-cellular matrixes (ECM) decreasing and hepatocyte protection. Low dose of SST (50μg•kg^(-1)•d^(-1) may be the optimum one among all doses.