基于MeCP2甲基化调控枯否细胞分泌炎症因子的栀子苷抗肝纤维化机制研究

项目名称： 基于MeCP2甲基化调控枯否细胞分泌炎症因子的栀子苷抗肝纤维化机制研究

项目编号： No.81202978

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 马陶陶

作者单位： 安徽医科大学

项目金额： 23万元

中文摘要： 栀子苷作为一种环烯醚萜苷,是中药栀子的主要药效成分。申请人前期研究发现，栀子苷对炎症及相关性疾病具有良好的疗效，在针对肝纤维化的治疗中发现栀子苷可有效抑制α-SMA、Collagen I表达，促进PPARγ的表达，进一步研究发现栀子苷可明显抑制甲基CpG结合蛋白MeCP2的表达；并且栀子苷预处理RAW24.7细胞可明显抑制LPS刺激引起的TNF-α、IL-1β等细胞因子的释放。本项目拟在高脂乳剂复合因素诱导的肝纤维化模型中继续确认栀子苷的疗效；以Kupffer细胞为靶细胞，研究栀子苷对Kupffer细胞分泌炎症因子的影响，并且通过研究PPARgamma的甲基化状态与MeCP2表达、NF-κB活性及IKKα、IKKβ磷酸化表达的相互关系，揭示栀子苷影响肝纤维化大鼠Kupffer细胞分泌细胞因子的机理及其相关信号通路。本项目旨在寻找栀子苷可能的细胞内作用靶点，探讨栀子苷抗肝纤维化的作用机制。

中文关键词： 炎症；巨噬细胞；MeCP2；栀子苷；信号通路

英文摘要： Geniposide is the main component of Gardenia jasminoides which is a sort of iridoids. It was reported that geniposide had good effects on inflammation and its related diseases. In the treatment of liver fibrosis, geniposide can effectively inhibit the expressions of α-SMA,Collagen I and promote the expressions of PPARgamma. It was demonstrated that geniposide could inhitbit the expressions of MeCP2 in our further research. Meanwhile it was found that geniposide inhibited the secretion of inflammatory cytokines such as TNF-α、IL-1βinduced by LPS in RAW264.7 cell line. The project will intend to invesigate the effects of geniposide in the liver fiborosis disease model induced by composite factors of high-fat emulsion and the regulatory effects of geniposide in the process of the inflammatory cytokines' release in Kuffer Cell in liver fibrosis. It also plan to consider the relationship between the methylation of PPARgamma and the expressions of MeCP2、the active of NF-κB and the posphorylations of IKKα、IKK. This study was conducted with the objective of evaluating the molecular mechanisms of geniposide efficiency in the secretion of inflammatory cytoines in kuffer cell and related signal pathways. This project can not only provide a potential cell targets for geniposide but also a valuable experimental exploration f

英文关键词： inflamation；macropahge；MeCP2；geniposide；signal