树豆酮酸A衍生物XJ-60通过抑制SP1/TGF-β/Smad3信号轴改善非酒精性脂肪肝病小鼠的肝纤维化

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Abstract：ObjectiveToinvestigatethemechanismofXJ-60，aderivativeofcajanonicacidA，forallviatingliverfibrosisin mice with non-alcoholic fatty liver disease （NAFLD）.Methods Twelvedb/db mice wererandomized equallinto NAFLD model group and XJ-60 treatment group with daily gavage of 50mg/kg XJ-60，with 6 db/m mice serving as the control group. Successfl modeling of NAFLDwasValidated using HEandOilRedOstaining andbymeasuring ALTand ASTlevels of the mice.Immunohistochemistrywasused fordetectinghepaticexpresionsof specific protein1 （SP1）and fibronectin （FN）;the changesinhepaticexpressonsofepithelal-mesenchyaltransition （EM）markers，extracellularmatrix （ECM）markersnd IL-6 weredetectedusing WestenblottingandEISA.InAM12cellinducedwithfreefattacids（FFA），theefectofXJ-60on expressions of SP1， transforming growth factor- ⋅β （TGF-β）， Smd3 /p -Smad3，and themarkersof EMTand ECMwereanalyzed. SP1knockdown experiment wasperformed to validate theroleofTGF-β/Smad3 signalingaxis in NAFLD.ResultsXJ-60 treatmentigantyuedlipdeelsrovederstologdowedatic6pesindce. Theexpression level of SP1 was positively correlated with α -SMAand negativelywith E-ca expression.InAML12 cells，XJ-60 treatmentat 10μmol/L significantly reduced FFA-induced lipid accumulationand downregulated cellular expressionsof SP1， TGF-β， p Smad3，and the EMTand ECMmarkers;SP1knockdown obviously inhibited the expressonlevelsof TGF-β，Smad3

and ECM markers.Conclusion XJ-60 ameliorates liver fibrosis and steatosis in mice with NAFLD possibly through SP1-mediated inhibition of the TGF-β/Smad3 pathwaytoreduceECMdeposition.

Keywords： non-alcoholic fatty liver disease; specific protein1;transforming growth factor-β;Smad3protein; cajanonicacidAderivative

非酒精性脂肪肝病（NAFLD）是全球最常见的慢性肝病，可促进约 25% 的成年人发展为肝纤维化、肝硬化和肝癌。（剩余19686字）