Preventive Effects Of JieJiuFuFang Against Liver Fibrosis Of Rats With Alcoholic Fatty Liver And The Involving Mechanisms

Alcoholic liver disease is characterized by the liver damage induced bysubstantive and chronical alcohol ingestion. The incidence of alcoholic liverdisease is increasing in China during the recent years, which results in itssecond position just under virus hepatitis in liver diseases. Fatty liver diseaseis a clinic syndrome that the pathological changes mainly appeared in liverlobule, where the liver cells suffer diffuse fatty degeneration. The diagnosiscriteria of fatty liver is that lipid content is over 5% of liver wet weight, orthere are over 30% of liver cells suffered fatty degeneration in each unit areaof tissue section under light microscope.Pure alcoholic fatty liver may be completely recovered if it could bedetected in early stage and be treated in time. On the contrary, it could developinto fatty hepatitis, fatty liver fibrosis and even liver cirrhosis, where it isdifficult to recover the pathological changes. Thus, it is important to prevent ortreat fatty liver and liver fibrosis in early stage.The formation of liver fibrosis is complicated, in which hepatic satellitecell (HSC), transforming growth factor (TGF-β1) and platelet-derived growthfactor (PDGF) have been paid much attention. HSC activation is the cellularbasis for liver fibrosis and the central substance of the production ofextracellular matrix. The increased production of extracellular matrix may beinduced by the activation and proliferation of HSC, which is a direct cause ofliver fibrosis. PDGF may promote the proliferation and migration of HSCthrough binding with the receptors on HSC, and also induce the production ofsome cytokines such as TGF-β1. TGF-β1 is a cytokine with its strongestability to induce collagen synthesis. TGF-β1 can promote the production ofextracellular matrix while inhibit its degradation, and induce HSC toproliferate indirectly. Therefore, for the prevention or therapy of liver fibrosis,it is important to inhibit or decrease HSC activation and decrease TGF-β1 andPDGF expression.Hereto, there is no the differential remedy for alcoholic fatty liver andliver fibrosis yet. By contraries, owing to the relatively little side effects,Chinese traditional medicines have the broad future of application anddevelopment. The synthetical effects are usually produced by Chinesetraditional medicines applied in the preventive and therapeutic treatmentagainst alcoholic liver disease. There are numerous activated components inChinese traditional medicines, which permit that they could regulate the bodyphysiological reactions to keep a balance. This superiority makes Chinesetraditional medicines become a new hope for the treatment of fatty liver andliver fibrosis. Nevertheless, there is still not a remedy of Chinese traditionalmedicines that possesses the effective curative effects on alcoholic liverdisease. Furthermore, there are numerous experimental and clinic studiesabout the preventive and therapeutic treatment of Chinese traditionalmedicines against alcoholic liver disease, but they usually limit to the curativeeffects but not the involving mechanisms. According to the theories andmodern pharmacological studies about Chinese traditional medicine, theauthor designed the remedy JieJiuFuFang (JJFF), which could promotealcohol degradation and benefit gall bladder, liver and spleen. The modernpharmacological studies have shown that some compositions of this remedypossessed the effects in improving ethanol metabolism, protecting liver cellsand decreasing serum concentration of biochemical marks of liver fibrosis.The clinical studies have proven that JJFF has the protective effects on liver,and it also could decrease the serum concentration of liver fibrosis marks, butthe involving mechanism is still not elucidated.In this study, we fed rats orally with alcohol and high fatty and iron feedto create the alcoholic fatty liver models. JieJiuFuFang or KaiXiLai wassupplemented by gastric gavage to model rats. Liver function, collagendeposition in liver tissue, liver hydroxyproline content, HSC activation,TGF-β1 and PDGFB expression and liver oxidative stress were evaluated byusing Western Blotting, immunohistochemistry staining, RT-PCR andbiochemical techniques. The following conclusions have been obtained in thisstudy:1. JJFF could significantly decrease the collagen deposition andhydroxyproline content in liver of rats with alcoholic fatty liver disease,suggesting JJFF has the preventive or inhibitive effects against alcoholic liverfibrosis.2. JJFF could significantly decrease α-SMA expression in liver of ratswith alcoholic fatty liver disease, suggesting its preventive effects against liverfibrosis.3. JJFF could significantly down-regulate TGF-β1 expression in liver ofrats with alcoholic fatty liver disease at both transcriptional and translationallevels, suggesting its preventive effects against liver fibrosis.4. JJFF could significantly down-regulate PDGFB expression in liver ofrats with alcoholic fatty liver disease at both transcriptional and translationallevels, suggesting its preventive effects against liver fibrosis.5. JJFF could significantly augment GSH-Px and SOD activities andreduce MDA content in liver of rats with alcoholic fatty liver disease,suggesting that JJFF could decrease liver oxidative stress.6. JJFF could significantly decrease the contents of ALT, AST and GGT inliver of rats with alcoholic fatty liver disease, suggesting that JJFF has theprotective effects on liver cells.7. JJFF could significantly decrease the contents of TG and TC in serumand TG in liver of rats with alcoholic fatty liver disease, suggesting that JJFFhas the regulative effects on fat metabolisms of liver cells.Altogether, these results suggest that JJFF has effective preventive effectsagainst liver fibrosis of rats with alcoholic fatty liver disease. The involvingmechanisms are mainly exhibited as decreasing liver oxidative stress,down-regulating gene expression of TGF-β1 and PDGF and consequentlyinhibiting the activation and proliferation of HSC. The decreased geneexpression of TGF-β1 and PDGF weakened the functions of collagen, whichmay be also involved in the preventive effects of JJFF, but further studies arerequired to confirm this hypothesis. Furthermore, this study also confirmed thetherapeutic effects and potential preventive effects of KaiXiLai againstalcoholic fatty liver.