目的 研究鸦胆子苦醇对类风湿关节炎（rheumatoid arthritis, RA）成纤维样滑膜细胞（fibroblast-like synoviocytes, FLS）细胞骨架力学性质的调控以及对RA FLS侵袭行为的影响。方法 细胞骨架染色法检测鸦胆子苦醇对RA FLS细胞骨架力学性质的调控；Transwell小室法检测鸦胆子苦醇对RA FLS细胞骨架的调控和对RA FLS侵袭行为的影响；酶谱和Western blotting法检测鸦胆子苦醇对RA FLS中MMP-2、MMP-3表达的影响。结果 通过细胞骨架染色并在显微镜下观察发现，鸦胆子苦醇可显著减少RA FLS伪足数量的产生，通过调节细胞骨架网络的力学性质抑制细胞的运动能力，鸦胆子苦醇可抑制RA FLS的侵袭并能下调MMP-2、MMP-3的表达水平。结论 鸦胆子苦醇能调节RA FLS的细胞骨架的力学性质并抑制细胞的侵袭行为，同时鸦胆子苦醇可通过降低MMP-2、MMP-3的表达抑制RA FLS的侵袭。研究结果为进一步开发治疗RA的新药物提供了相应实验依据。

Objective To investigate the effects of brusatol on mechanical properties of the cytoskeleton as well as the invasion behavior of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Methods Cytoskeleton staining method was used to determine the regulatory effects of brusatol on mechanical properties of the RA FLS cytoskeleton. Transwell chamber assay was used to detect the effects of brusatol on the cytoskeleton and invasion behavior of RA FLS. The effects of brusatol on the expression of matrix metalloproteinase-2/3 (MMP-2/3) of RA FLS were measured by zymography and Western blotting methods. Results Cytoskeleton staining and microscope observation showed that brusatol could significantly reduce the formation number of RA FLS pseudopodia, thus inhibited cell movement ability via regulating mechanical properties of cytoskeleton. The invasion behavior of RA FLS was inhibited by brusatol, and brusatol could down-regulate the expression of MMP-2/3. Conclusions Brusatol plays an important role in regulating mechanical properties of cytoskeleton and inhibiting the invasion behavior of RA FLS. Meanwhile, brusatol can inhibit the invasion behavior of RA FLS through down-regulating the expression of MMP-2/3. The research findings provide the corresponding experimental basis for further development of new drugs for RA treatment.

国家111计划项目（B06023），国家自然科学基金项目（11532004，31270990）