病灶中结核分枝杆菌的彻底杀灭与清除是结核病治愈的核心与关键。一线抗结核药物由于自身结构及药代动力学特点，常规剂型难以穿透骨髓-血屏障、无法在脊柱结核病灶长期存留和有效渗透，致使抗结核疗效不佳。基于前期国家自然科学基金研究基础，本研究拟采用现代基因工程与制药技术，制备巨噬细胞外泌体负载结核分枝杆菌免疫调节特异性micRNAs和利福平的新型载药系统。通过提取巨噬细胞外泌体，使其转染促进细胞凋亡与自噬、发挥免疫调节作用的结核分枝杆菌特异性miRNAs并装载利福平，用于兔脊柱结核模型的治疗，探索该载药外泌体在脊柱结核病椎的靶向性及作为细胞内载体与病灶巨噬细胞间跨膜转运、清除和杀灭结核菌的作用机制；同时观察该新型药物输送系统治疗兔脊柱结核的效果。本研究以靶向病灶高效杀菌以及基因转运免疫调节为治疗手段，对于脊柱结核的快速、高效治愈具有重要意义。新型药物输送系统的开发也为临床治疗脊柱结核提供一种新思路。

Mycobacterium tuberculosis’clearance of the focus is the key for tuberculosis’ cure. First-line antituberculosis-drug like rifampicin and isoniazid,because of its structure and pharmacokinetics,the conventional agent is difficult to penetrate the bone marrow-blood barrier and retent in the focus of spianal tuberculosis,resulting in poor efficacy of antituberculosis.Based on our studies of pregrants of national natural science foundation,the present study is going to develop a novel drug-loading system for macrophage exosomes-loaded rifampicin and Mycobacterium tuberculosis immunomodulatory specific-micRNAs. Through the preparation of macrophage exosome,the load of Mycobacterium tuberculosis specific-miRNA molecules which promote apoptosis and autophagy and fat-soluble rifampicin in exosome,the following antituberculosis therapy of rabbit spinal tuberculosis with developed exosome,to explore exosome medicine’s targeting in pathologic vertebrae and its transmembrane tansport as well as the mechanism towards clearance and killing of Mycobacterium tuberculosis. Meanwhile,the effect of the new drug delivery system for the treatment of rabbit spinal tuberculosis is also observed.The study has great advantages for spinal tuberculosis’cure, including the targeted gene therapy and immunomodulatory,efficient antituberculosis within and without the macrophage,improvement of overall compliance to chemotherapy and the less side effects of drugs.It might provide a new way for the clinical treatment of spinal tuberculosis.