结核病灶中的肿瘤坏死因子α(TNF-α)可诱发炎症和破骨细胞活化，加速骨溶解；并且诱导免疫病理反应,在结核核心病灶周围形成致密肉芽肿。我们的前期研究证实结核肉芽肿及其周边的椎骨硬化形成可导致病椎骨髓-血屏障异常，严重影响一线抗结核药物的组织穿透，致使疗效不佳。基于前期国家自然科学基金研究基础，本研究拟采用现代纳米技术和局部靶基因沉默生物技术，制备一种复合TNF-a siRNA 的INH RFP羟基磷灰石纳米骨，通过对复合材料的生物力学、体内外降解与释药、病灶局部基因沉默效应以及兔脊柱结核模型治疗的研究，探索TNF-αsiRNA对病椎病理性骨髓-血屏障形成机制的影响以及缓释纳米粒在病椎局部的靶向性和穿越骨髓-血屏障的转运机制，同时观察该复合纳米骨治疗兔脊柱结核的效果。此研究对于通过局部抗结核治疗实现快速治愈病灶和病椎结构性重建有重要意义，为临床治疗脊柱结核提供一种新的思路。

Tumor necrosis factor-α plays an important role in inducing inflammation and osteoclasts' activation, which might accelerate osteolysis and lead to immunopathogenesis of granulumatous formation in the focus of tuberculosis. Our early study had demonstrated that anomaly of bone marrow-blood barrier caused by granulumatous formation and bone sclerosis prevents the biodistribution of first line antituberculosis drugs from normal vertebrae to focus and lead to the bad effects of antituberculosis therapy. Based on the studies of our pre grants of national natural science foundation ,the present study is going to develop a new nano- composite bone which combined with tumor necrosis factor-a(TNF-a) siRNA , namoparticles of isonicid and rifampin and hydroxyapatite ceramic, through the vitodynamics ,the release kinetics of in vitro and in vivo, the gene silencing effect and the therapeutic research of rabbit spinal tuberculosis, to explore the influences of TNF-a siRNA on bone marrow-blood barrier and the nano-medicine's targeting in pathologic vertebrae and its transport mechanism at marrow-blood barrier, meanwhile, the therapeutic effects of rabbit spinal tuberculosis is also observed. The study has great significance for the regional management of spinal tuberculosis, including the fast cure of focus and good reconstruction of pathologic vertebrae. It might provide a new thinking of improving effects, decreasing relapse of focus and deformity of diseased vertebral segment for the treatment of spinal tuberculosis.