基于Wnt/β-catenin信号通路研究当归补血汤调控造血干细胞促进造血重建的机制及中医"气血相生"的机理

项目名称： 基于Wnt/β-catenin信号通路研究当归补血汤调控造血干细胞促进造血重建的机制及中医"气血相生"的机理

项目编号： No.81202634

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： 姚重华

作者单位： 上海中医药大学

项目金额： 24万元

中文摘要： 骨髓抑制是大多数免疫抑制剂共有的不良反应，骨髓造血干细胞的过度凋亡是影响造血重建的主要因素，而Wnt/β-catenin信号通路直接调控造血干细胞的凋亡。 本课题组在建立小鼠骨髓造血干细胞凋亡、骨髓抑制模型及证实当归补血汤能抑制小鼠骨髓造血干细胞凋亡、调控Wnt及其受体表达的基础上，通过R Spondin-1、LiCl和Dickkopf-1、Frz蛋白的干预，采用定量RT-PCR、Western Blot等技术，检测Wnt及其下游Dsh、GSK3β、Axin、APC、β-catenin信号分子基因、蛋白的表达，深入研究骨髓造血干细胞内Wnt/β-catenin信号转导过程，观察当归补血汤及其拆方（益气法、补血法）调控该信号转导通路的作用靶点，阐明当归补血汤介导该信号通路促进造血重建的机制及中医"气血相生"的分子机理，为中医药防治骨髓抑制提供更确切的方法，为中医"气血相生"理论提供实验依据。

中文关键词： 当归补血汤；造血干细胞；信号转导；Wnt；气血相生

英文摘要： Bone marrow depression is the commonly adverse reaction of the most immunodepressant. The apoptosis of Bone marrow Hematopoietic Stem Cell, which is regulated directly by the Wnt/β-catenin signal pathway, is the chief factor to the hematopoietic reconstitution. Base on established bone marrow Hematopoietic Stem Cell apoptosis mice model and bone marrow depression model, and confirmed that Danggui Buxue Decoction can depress the apoptosis of mice bone marrow Hematopoietic Stem Cell and regulated Wnt and it's acceptor, we would like to use R Spondin-1、LiCl and Dickkopf-1、Frz protein for intervention, to test the expression of signal molecules gene、protein such as Wnt、Dsh、GSK3β、Axin、APC、β-catenin by the technology of RT-PCR and Western Blot. In order to study the signal transduction process of Wnt/β-catenin deeply and systematically, and identify specific function target point of Danggui Buxue Decoction and it's different composition on this transduction, meanwhile, clarify the mechanism of Danggui Buxue Decoction's role on the promote the realignment of hematopoiesis and the traditional chinese medicine theory of "Qi and Blood generate each other", provide more exactly methods for chinese medical prevention and treatment on bone marrow depression which is caused by immunodepressant, and offer basis for traditiona

英文关键词： Danggui Buxue Decoction；Hematopoietic Stem Cell；Signal Transduction；Wnt；Qi and Blood generate each other