铈NPs夹心离子共敏化介孔硅纳米颗粒通过抑制ZIP8-Zn-MTF1轴调控类风湿关节炎巨噬细胞极化的机制研究

类风湿关节炎（RA）最重要的发病机制是滑膜炎症性病变，但其具体机制尚不明确。近年已发现滑膜巨噬细胞极化、锌稳态失衡在RA发病机制中均起到重要作用。本研究计划构建一种新型的CeO2介孔硅纳米颗粒（CeO2@MSN），并将II型胶原蛋白抗体修饰于其表面，承载于水凝胶微球，将其注射到胶原诱导关节炎动物模型的关节腔中观察其治疗效果，并检测在锌代谢稳态中起重要作用的ZIP8-Zn-MTF1轴在该介孔硅颗粒租用下发生的变化及其相应的分子机制，观察锌代谢在此过程中发生的变化并总结其规律。同时，在体外细胞模型研究中，通过对ZIP8-Zn-MTF1轴的调控，观察巨噬细胞极化所发生的改变及其分子细胞生物学过程，从而研究RA滑膜巨噬细胞极化改变的规律和具体机制，并明确CeO2@MSN治疗RA的潜在原理，进一步探究RA滑膜炎性病变的机制，为探索RA的发病机理和潜在的治疗靶点提供新的理论基础。

Inflammatory lesions of the synovium is the most important pathogenesis of rheumatoid arthritis (RA), of which the specific mechanism is still unclear. In recent years, it has been found that the polarization of synovium macrophages and the homeostasis imbalance of zinc metabolism play important roles in the pathogenesis of RA. The present project aims to build a novel CeO2 meso-porous silicon nanoparticles (CeO2@MSN) and modify type II collagen antibodies on their surfaces, carrying them in hydrogel microspheres, and injecting them into the joint cavity of collagen-induced arthritis animal models. The therapeutic effect, as well as the changes and corresponding molecular mechanisms of ZIP8-Zn-MTF1 axis which played an important role in zinc metabolic stability, would be observed, with the changes of zinc metabolism in this process and the corresponding regularity. Meanwhile, in the study of in vitro cell models, with changes in the regulation of ZIP8-Zn-MTF1 axis, the macrophage polarization and their molecular cell biologic process will be observed, so as to study the specific mechanism of RA synovium macrophage polarization, in order to clarify the potential principle of CeO2@MSN in the therapy of RA, to further explore the mechanism of RA synovium inflammatory lesions, and to provid a new theoretical basis for the pathogenesis and potential therapeutic targets of RA.