莱姆关节炎中关节细胞因子微环境失调的机制及雪胆甲素的调节作用研究

莱姆病是由伯氏疏螺旋体感染引起的人兽共患病。中晚期莱姆病主要表现为莱姆关节炎、神经系统炎症和心脏炎，其中莱姆关节炎发生率最高，危害最大，但发生机制未充分阐明。关节组织形成了独特的区域免疫微环境，并与关节炎的发生发展紧密相关。我们的前期研究表明，细胞因子在莱姆关节炎发病机制中有重要作用，但是既往对关节局部细胞因子微环境系统性评估的研究未见。现在我们提出新的假说：莱姆螺旋体通过其表面蛋白调控关节细胞因子微环境，导致关节炎症的发生发展。为此，我们拟用莱姆螺旋体标准菌株及其重组表面蛋白BmpA进行系列研究，应用莱姆关节炎不敏感、中度敏感和高敏感小鼠建立动物模型，用转录组、蛋白组和细胞因子芯片，从不同层次探索莱姆螺旋体诱发关节细胞因子微环境失调、引发关节炎的机理及云南独特天然产物雪胆甲素对关节细胞因子微环境失调的调节作用。通过上述研究，为莱姆关节炎防治提供理论依据和新思路。

Lyme disease is a zoonosis caused by the infection of Borrelia burgdorferi，and is mainly manifested as Lyme arthritis, nervous system inflammation and cardiac inflammation. The incidence of Lyme arthritis is the highest, but its pathogenesis is not fully clarified. Joint tissue forms a unique regional immune microenvironment, which is closely related to the development and development of arthritis. Our previous studies show that cytokines play an important role in the pathogenesis of Lyme arthritis, but the systematic evaluation of local cytokine microenvironment in joints have not been done yet in previous studies. Now we propose a new hypothesis: Lyme spirochetes can regulate the joint cytokine microenvironment through its surface proteins, attract inflammatory cells and lymphocytes to to the joints, leading to the development of joint inflammation. To this end, we intend to use Lyme spirochetes standard strains and its surface protein BmpA, to establish animal models of Lyme arthritis with non-sensitive, moderately sensitive and high sensitive mice strians and apply transcriptome, proteome and cytokine chip\ from different levels to explore joint cytokine microenvironment disorders induced by Lyme spirochetes, the regulation mechanism of Yunnan unique natural product hemslecin A. The above research will provides the scientific basis and new ideas for the prevention and treatment of Lyme arthritis.