Wnt/β-catenin信号对结核分枝杆菌感染后巨噬细胞自噬调控机制研究

巨噬细胞与结核分枝杆菌相互作用后发生的自噬对结核病的发生、发展及预后具有重要影响。但是，该过程涉及的信号通路十分复杂，其调控机制尚未阐明。近年研究表明，Wnt/β-catenin信号通过调控宿主细胞自噬参与多种疾病的发生发展过程。但其对结核分枝杆菌感染后巨噬细胞的自噬调控尚未见相关报道。 . 基于以上研究背景，本项目通过激活和阻断结核分枝杆菌感染后小鼠巨噬细胞的Wnt/β-catenin信号，探讨该信号对结核分枝杆菌感染后细胞自噬的调控作用。并进一步用Rapamycin和LiCl来研究该信号对自噬诱导环节的调控是依赖于mTOR-dependent还是mTOR-independent途径。并过表达自噬启始和膜延伸环节的关键基因Beclin1和Atg5，同时用小鼠体内试验验证，最终阐明Wnt/β-catenin信号对自噬的调控机制，并为结核病的预防及靶向药物研制提供理论依据。

The autophagy of macrophage post infection with Mycobacterium tuberculosis Mtb has an important impact on the pathogenesis and outcome of tuberculosis. However, due to the complex signaling pathways involved in this biological process , the mechanism has not been well elucidated. Emerging evidence shows that Wnt/β-catenin signal involved in pathogenesis of diverse diseases through regulating autophagy of target cell. Whether Wnt/β-catenin signal is involved in regulating the autophagy of macrophage infected with Mtb remains unknown. . In the present study, firstely, we will explore the regulation of Wnt/β-catenin signaling pathway on the autophagy of macrophage with active or inhibitive Wnt/β-catenin signal and infection of Mtb. Then, Rapamycin and LiCl are employed to examine whether the mTOR-dependent or mTOR-independent pathway will involve in the autophagy process . And over expressed vector of Atg5 and Beclin1 are employed to examine the autophagy pathway regulated by Wnt/β-catenin signal. And our datas will reveal the mechanism of Wnt/β-catenin signal on the autophagy mechanism of the macrophages. It will provide a new insight into the theory basis for development of targeted drugs of tuberculosis .