类风湿关节炎（RA）是以滑膜组织的过度增生、血管翳形成和骨侵蚀为病理特征的慢性自身免疫性疾病。近年来研究发现成纤维样滑膜细胞（FLS）的异常增殖和凋亡不足在RA发病中起关键作用。土家族药物枫杨临床用以治疗RA疗效确切，项目组前期研究发现枫杨醇提物具有很好地促RA-FLS凋亡效果，并通过提取分离获得有效成分群枫杨总黄酮。因此，课题组结合预实验结果，提出“枫杨总黄酮可以通过Fas/FasL途径介导的线粒体通路促进RA-FLS凋亡，调控其异常增殖”的科学假说。现拟结合药理学、分子生物学等多学科研究手段，采用siRNA转染技术、CRISPR-Cas9 System靶向基因敲除技术、免疫荧光和亚细胞蛋白免疫印迹法、荧光探针等先进技术，从动物、细胞、分子生物学水平等不同水平，深入探讨枫杨总黄酮通过调控Fas/Fasl途径介导的线粒体通路，促进其凋亡以治疗RA的分子作用机制。

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by excessive proliferation of synovial tissue, pannus formation and bone erosion. Recent studies have found that abnormal proliferation and inadequate apoptosis of fibroblast-like synovial cells (FLS) play a key role in the pathogenesis of RA. Tujia medicine Pterocarya has a good treatment efficacy for RA. Previous studies of our research group found that the alcohol extract of Pterocarya has a good effect on promoting the apoptosis of RA-FLS. The total flavonoids of Pterocarya were obtained by extraction and separation. Therefore, combined with the preliminary experimental results, the group proposed the scientific hypothesis that total flavonoids of Pterocarya can promote the apoptosis of RA-FLS and regulate its abnormal proliferation through the Fas/FasL pathway-mediated mitochondrial pathway. Combining with pharmacology, molecular biology and other research methods, using advanced technologies such as siRNA transfection technology, CRISPR-Cas9 System targeted gene knockout technology, immunofluorescence and subcellular protein immunoblotting, fluorescence probe, etc., to explore the molecular mechanism of total flavonoids of Pterocarya, which can inhibit the secretion of inflammatory factors by RA-FLS and promote its apoptosis to treat RA by regulating the mitochondrial pathway mediated by Fas/Fasl pathway, so as to provide scientific basis for further development and utilization of Tujia medicine.