PKB/AKT1介导的结核杆菌感染及防治的分子机制研究

项目名称： PKB/AKT1介导的结核杆菌感染及防治的分子机制研究

项目编号： No.30871117

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： 范红

作者单位： 四川大学

项目金额： 31万元

中文摘要： 本课题对PKB/AKT1信号通路在防治结核病的过程进行了研究，为结核病的控制提供了新的思路。先期使用H37Ra感染THP-1细胞，未发现明显差异；接着通过构建ESAT-6蛋白，虽然成功构建了蛋白，但是由于ESAT-6纯化效率较低，无法达到我们实验的结果，且已有相关文献报道相应实验结果，故未再使用。通过复习文献，我们调整思路从体内研究PKB/AKT1在结核病中的关系。 我们的研究发现， PKB/AKT1信号通路及其相关因子基因突变与结核病的发病有关系： PKB/AKT1信号通路关键基因AKT1基因多态性与结核病的发病密切相关，该通路下游免疫炎症因子IL-18，MCP-1、IL-10基因多态性与结核病的发病也相关。基于本研究的思路，我们通过复习文献，对结核病的相关研究进行系统分析，发现PKB/AKT1信号通路下游免疫炎症因子IFN-γ12289;SLC11A1、MCP-1基因是结核病的易感基因。本研究的结果为结核病的防治提供了新的理论依据，PKB/AKT1信号通过及其关键因子AKT1可能成为结核病防治的靶点。

中文关键词： 结核；PKB/AKT1；通路；靶点

英文摘要： In this project, due to biological safety limitation of the laboratory, we first infected THP-1 cell with H37Ra, and investigated the association between the AKT1 pathways with H37Ra. However, we didn’ found significant difference. Then we constructed the protein ESAT-6 and were aimed to use that protein to stimulus the THP-1 cell. Although we succeed to construct it, however, we didn’ purify it easy to use to stimulus the THP-1 cell. In addition, there is a same results used the ESAT-6 and THP-1 cell. So we reviewed the researches and change our mind. Then we analyzed the PKB/AKT1 pathways in vivo. Our results showed that the genetic variants of the PKB/AKT1 pathways genes were significant associated with the risk of TB. The genetic variant in AKT1 gene is significant associated with increased risk of TB. In addition to AKT1 gene, some inflammatory genes such as IL-18, il-10 and MCP-1 were also associated with the risk of TB. Based the research way of the project, we reviewed all genetic variants of TB, and found the IFN-r, SLC11A1 and MCP-1 genes were the TB susceptible genes. In summary, in this project we found the PKB/AKT1 pathway is associated with TB, and AKT1 may be took as a genetic target for the treatment of TB.

英文关键词： tuberculosis；PKB/AKT1；pathway；target