Effects And Eechanisns Of Acrcmoniumterricola Milleretal Mycelium On Immunological Hepatic Fibrosis Induced By Porcine Serum

Objective To clarify the protective effects of Acremoniumterricola milleretalmycelium(AMM) on immunological hepatic fibrosis rats induced by porcine seurm andits mechanism.Methods Adult healthy of SD male rats were randomly divided into the following sixgroups, including normal control group, liver fibrosis model group, colchicinesgroup(0.1mg/kg) and AMM(700,350,175mg/kg) treated groups. Establishing a ratmodel of liver fibrosis by giving an intraperitoneal injection of porcine seurm (0.5ml,twice a week)for18weeks. Except for normal control group with same volume ofnormal saline.The drug was given by intragastrically in AMM group and colchicinesgroup respectively, and rats in the normol control group and model group were givenwith same volume of distilled water. Weigh the rats and calculate the liver, spleen index.HE and VG staining were used to examine the histopathological change. The activity ofALT、AST and the concent of HA, LN, PCⅢ, TGF-β1in sera were measured bycommercial kits. The concent of Hyp, MDA and the activity of SOD, GSH-PXinhepatic tissue were measured also by commercial kits. The expression of TGF-β1andα-SMA protein in the liver tissues was assayed by immunohistochemistry. Theexpression of p-Smd2/3and Smad7in TGF-β/Smad signal transduction pathways wasassayed by western blot.Results: Research findings, when administered PS for18weeks, the weight of modelgroup rats were significant lower than those in control group. We found that the liverindex and spleen index were significant rise in model group rats, AMM（350,700mg/kg）different degree of reducing the weight, liver index and spleen index. We found that the serum levels of AST and ALT were increased in the model group with respectto control group, but no significance. Similarly, AMM (350,700mg/kg) slightlyreduced the levels of AST and ALT with respect to model group, but also nosignificance. We found that the activity of SOD and GSH-Px in model group weresignificantly lower than those in control group, but the content of MDA in the livertissue was significantly increased; AMM（350,700mg/kg）different degree of reducingthe content of MDA and elevating the activity of SOD, GSH-Px in the liver tissue. Wefound that HA, LN, PCⅢ,Hyp content and the expression of α-SMA were markedlyincreased in the model group compared to the control group; AMM(350,700mg/kg)obviously reduced the content of HA, LN, PCⅢ,Hyp and the expression of α-SMAcompared to the model group. HE staing showed that the structure of liver tissues wasnormal in the control group rats and no remakable changes were found. A smallnumbers of inflammatory cells was found around the portal area and central veinwithout obvious hepatocyte necrosis in model group.VG staing showed that extensivered accumulation of collagens in the liver tissues. Most of the fibrosis developed aroundcentral veins, and complete septal fibrosis was observed, even in some serious unitsfalse lobules presented. AMM（350,700mg/kg）treatment significantly decreasedfibrotic deposits and fibrosis score, the structure of liver tissues was almost normal. Theexpression of TGF-β1in serum and tissue were significantly increased, also a higherexpression of p-Smd2/3, but Smad7was decreased in the model group. AMM（350,700mg/kg）significantly suppressed the express of TGF-β1, α-SMA and p-Smd2/3, butincreased the expression of Smad7in liver tissue of IHF model group rats.Conclusion AMM has significantly against immune-mediated liver fibrosis in rats, andits mechanisms might be associated with its ability to reduce oxidative stress, inhibitcollagen synthesis and block TGF-β/Smad signaling pathway.