Galectin-3对肝星状细胞激活及凋亡的影响

项目名称： Galectin-3对肝星状细胞激活及凋亡的影响

项目编号： No.30872498

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 李涛

作者单位： 北京大学

项目金额： 28万元

中文摘要： 肝星状细胞（HSC）和枯否细胞（KC）间通过细胞因子TGF-β30340;旁分泌和自分泌作用在HSC的激活和肝硬化门静脉高压症的发生发展过程中具有重要的作用。研究发现，TGF-β30340;这些作用可能是通过半乳糖凝集素-3（Galectin-3）实现的。本研究构建含H1启动子和绿色荧光蛋白基因的Galectin-3 RNA干扰载体。转染我们建立的大鼠HSC细胞系rHSC-99和体外培养的大鼠KC。建立rHSC-99和KC的共培养体系，观察通过Galectin-3调控HSC和KC间相互作用对HSC激活和凋亡的影响。然后建立大鼠的肝纤维化模型，通过门静脉系统转染RNA干扰载体，体内实验进一步探讨沉默Galectin-3基因能否减轻大鼠肝纤维化的程度。在体外和体内实验两个层面研究Galectin-3基因沉默阻断细胞因子的旁分泌和自分泌作用对HSC激活和凋亡的调控作用以及在肝纤维化发生发展中的作用。

中文关键词： 半乳糖凝集素-3；转化生长因子-β65307;肝星状细胞；激活；凋亡

英文摘要： Interactions between Hepatic stellate cell (HSC) and Kupffer cell (KC) which through Transforming growth factor-βTGF-βautocrine and paracrine process are key factor during the development of liver cirrhosis and portal hypertension. The function of TGF-βay be carried out by Galectin-3. In this study, we use RNA interference (RNAi) method. Galectin-3 RNAi vectors containing H1 promotor and green fluorescence protein was constructed and transfected into HSC cell line rHSC-99. The KC was isolated from rat, and then HSC and KC co-culture system was established to investigate regulation of HSC activation and apoptosis by interactions between HSC and KC which regulated by Galectin-3. Then, cirrhotic rat model was established and in vivo study was performed. This in vitro and in vivo study was designed to elucidate blockade cyokine autocrine and paracrine process through Galectin-3 gene silence in regulation of HSC activation an apoptosis, and provide a new way on therapeutic of liver fibrosis and portal hypertension.

英文关键词： Galectin-3; Transforming growth factor-βHepatic stellate cell; Activation; Apoptosis