The Protective And Therapeutic Effects Of Immunomodulaiing Peptide On Alcoholic Fatty Liver

Objective To study the protective and therapeutic effects of immunomodulatingpeptide (PGPIPN) on the treatment of Alcoholic Fatty Liver (AFL) in the animal andcell models.Methods1.60Kunming mice were randomly divided into six groups: control, model, HGP,PGPIPN Ⅰ, PGPIPN Ⅱ and PGPIPN Ⅲ groups. Mice were drenched with liquor tomake the model of AFL. The control group was given equal physiological saline. Thewhole experiment lasted12weeks. At the end of the experiment, the mice were killed tocollect the samples of serum and liver tissues. The liver index (LI) and spleen index (SI)were calculated. The contents of triglyceride (TG), total cholesterol (TC), low densitylipoprotein C (LDL-C) and high density lipoprotein C (HDL-C), and activities ofalanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayedin serum. The contents of TG and malondialdehyde (MDA), and activities ofsuperoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and adenosine5’-triphosphate（ATP）were also determined in liver homogenate. The pathologicalchanges of tissues were observed. Basic pathological changes of the mice wereobserved using routine HE staining and fatty degeneration of liver tissues was evaluatedby Oil red O staining under light microscope (LM).The expression of ATPase6,ACCand PPAR-γ were determined by RT-PCR and the protein expression of ACC andPPAR-γ were detected by western blot.2. The concentrations of alcohol inducing hepatocyte steatosis，were detected byMTT assay(0.3%、0.6%、1.2%、2.4%).The models of fatty degeneration LO2liver cellswere treated for same time with The optimum concentration of hovenia dulcis thumb extraeted lipuid.The accumulation of lipid droplets were observed by light invertedmieroscopy after red oil-O staining. An estimation of Releasing dose of alanineaminotransferase(ALT)，aspartate aminotransferase(AST) in the culture was detectedthrough automatic biochemical analyzer，and the intraeelluer triglyceride(TG) levelwould be determined by the kit.Results1. Effect of PGPIPN on the AFL animal model: PGPIPN could reduced the levelsof LI and SI, the activities of ALT and AST, and the contents of TG, TC, LDL-C. MDAin mice serum were remarkably decreased, the content of SOD, HDL-C, GSH-PX inmice serum was increased. Liver histopathological examination showed PGPIPN couldameliorate hepatic steatosis. Compared with control group, the expression of ATPase6and PPAR-γmRNA and PPAR-γ protein were decreased, on the contrary, the expressionof ACC mRNA and protein increased in model group; compared with model group, theexpression of ATPase6and PPAR-γ mRNA and PPAR-γ protein increased, theexpression of ACC was significantly lower in PGPIPN group in mice.（P＜0.01or P＜0.05）2．Effects of PGPIPN against ethanol-induced LO2cell damage: MTT showed thatcertain concentration of PGPIPN can ease the damage caused by AFL. The degree ofsteatosis and active fluoresce in PGPIPNⅠ,Ⅱ,Ⅲ group was lower than that of modelgroup, whereas the levels of ALT, AST, TGwere the similar.Conclusion1. PGPIPN may ease the liver damage in vitro and in vivo via the role of operatewith modulation of fat metabolism and reduction of lipid peroxidase.2. The protection of PGPIPN against AFL might be associated with the inhibitionof ATPase6、PPAR-γ and the expression of ACC was significantly lower.3. PGPIPN can interfere with the development of AFL,thus protecting liver cells.