Effects and Mechanisms of Acremoniumterricola milleretal mycelium on Liver Fibrosis Induced by Carbon Tetrachloride in Rats

摘要

Acremoniumterricola milleretal mycelium (AMM) is one of the most preciousntraditional Chinese medicines. It has numerous protective effects on organs, and has beennused in Chinese herb prescription to treat refractory diseases. Our preliminary studiesndemonstrated that AMM had hepatoprotective activity in acute liver injury. We furtherninvestigated the effects of AMM on liver fibrosis in rats induced by carbon tetrachloriden(CCl4) and explore its possible mechanisms. The animal model was established by injectionnwith 50% CCl4 subcutaneously in male Sprague-Dawley rats twice a week for eight weeks.nMeanwhile, AMM (175, 350 and 700 mg/kg) was administered intragastrically per day untilnsacrifice. We found that treatment with AMM (175, 350 and 700 mg/kg) decreasednCCl4-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagenntype III levels, and contents of hydroxyproline in liver tissues. It also restored thendecreased SOD and GSH-Px activities and inhibited the formation of lipid peroxidativenproducts during CCl4 treatment. Moreover, AMM (350 and 700 mg/kg) decreased thenelevation of TGF-β1 by 19.6% and 34.3%, respectively. In the pathological study, liverninjury and the formation of liver fibrosis in rates treated by AMM were improved significantly.nImmunoblot analysis showed that AMM (175, 350 and 700 mg/kg) inhibited Smad 23 phosphorylation, and elevated inhibitor Smad 7 expression. These results suggested thatnAMM could protect liver damage and inhibit the progression of hepatic fibrosis induced bynCCl4, and its mechanisms might be associated with its ability to scavenge free radicals,ndecrease the level of TGF-β1 and block TGF-β/Smad signaling pathway.