BML-111Protected Carbon Tetrachloride-induced Hepatic Fibrosis In Rats And The Possible Mechanisms

Objective：LXs are a class of newly found arachidonic acid metabolites, possesspotent anti-inflammatory and pro-resolution effects. We had previously confirmed theLXs agonists BML-111had possessed the protection effects for liver. Therefore, thisstudy we investigated the protection effect of BML-111on hepatic fibrosis and thepossible mechanisms.Methods：Sprague-Dawley（SD） rats were used to build experimental hepaticfibrosis via subcutaneous injection of CCl4. The degree of liver injury andinflammatory cell infiltration were observed by HE stain. AST and ALT activity inserum were tested to evaluate the liver function. The level of hepatic fibrosis wasconjunctively confirmed through general feature of liver, VG and Masson stain ofliver biopsy and content of Hyp. Western-blot and immunohistochemistry were usedto examine the expressions of α-SAM. The expression levels of TGF-β1and PDGFwere detected by ELISA and Western-blot. Western-blot was used to observe theexpression levels MMP-2, MMP-3, MMP-7, MMP-9and TIPM-1. The content ofMDA, activity of SOD, GSH-Px, and CAT, and the T-AOC were detected by reagentkits. The NF-κB p65nuclear translocation activation was observed by immunofluo-rescence.Results：（1）BML-111inhibited liver injury and inflammatory cell infiltration,and improved liver function.（2）BML-111could inhibited the degree of hepaticfibrosis.（3）BML-111repressed the activation of HSC.（4）BML-111reduced theexpression levels of TGF-β1and PDGF.（5）BML-111decreased the expressions ofMMP-2, MMP-3, MMP-7, MMP-9, and TIMP-1.（6） BML-111decreased thecontent of MDA, but increased the activity of antioxidase such as SOD,GSH-Px, andCAT, and enhanced T-AOC in liver tissue.（7）BML-111suppressed the translocationof NF-κB P65.Conclusion：BML-111played a protective role of experimental liver fibrosis inrats induced by CCl4. The possible mechanisms include down-regulation theexpressions of TGF-β1and PDGF, suppression the activation of HSC and reduction subsequently ECM expression, reversing the imbalance of MMPs/TIMPs in livertissue that regulating the abnormal ECM metabolism, recovering oxidant/antioxidantbalance of liver tissue in rats, and hindering NF-κB P65nuclear translocation.