摘要
目的探讨18α甘草酸(18αGL)对CCl4诱导的肝纤维化大鼠的I型胶原的调控作用。方法采用40%CCl4皮下注射方法建立肝纤维化大鼠模型,分为正常组、肝纤维化模型组和18αGL干预组。采用免疫组织化学和实时PCR分析I型胶原表达情况。Signal-Net网络分析发现与I型胶原组分COL1A1和COL1A2直接相关的基因,实时PCR分析18αGL干预后相关基因表达情况。结果 18αGL能够改善纤维化大鼠I型胶原相关COL1A1和COL1A2的mRNA水平,并且能减少I型胶原的分布。Signal-Net网络分析发现与COL1A1和COL1A2直接相关的基因中,与TGF-β/Smad、Rho/rock、MAPK、PDGF和MMP等信号通路相关,动物体内18αGL可引起RAC、RHOA、HSPB、SMAD3、SP-1和MMP2、MMP9转录水平的下调。结论 18αGL能够显著减少纤维化大鼠肝脏I型胶原的表达,并且从多通路抑制I型胶原COL1A1和COL1A2表达,从而可以多层次,多靶点的改善胶原和影响肝纤维化进程。
Objective To investigate the effect of 18α-glycyrrhizin（18αGL）on regulation of collagen I at transcription level in rats with experimental liver fibrosis.Methods Male SD rats were randomly divided into control group,fibrosis group and GL group.The model rats in fibrosis group and GL group were established by subcutaneous injection of 40% CCl4（twice a week）for 8 weeks.Immunohistochemical examination and real-time polymerase chain reaction（RT-PCR）were carried out to detect the expression of collagen I.The collagen I network was mapped by signal-net,and the mRNA levels of relative genes were evaluated by RT-PCR.Results 18αGL could inhibit CCl4-induced liver fibrosis,and decrease the content of collagen I as well as the mRNA levels of COL1A1 and COL1A2 in rat liver tissue.Using signalnet to map the collagen I network,TGF-β/Smad,Rho/rock,MAPK,PDGF and MMP pathway were found to regulate collagen I directly.In vivo,18αGL could down-regulated the levels of related moleculars,including RAC,RHOA,HSPB,SMAD3,SP-1 and MMP2,MMP9.Conclusion 18αGL markedly could inhibit collagen I with several signal pathway changes including TGF-β/smad,and might improve collagen expression and affect the process of liver fibrosis in a multilayered and multi-target way.
出处
《肝脏》
2015年第2期118-123,共6页
Chinese Hepatology
