Department of Anatomy, Anhui Medical University, 81 Meishan Road, Hefei 230032, China.
Grade 2016, The First Department of Clinical Medicine, Bengbu Medical College, 2600 Donghai Road, Bengbu 233030, China.
Int Immunopharmacol. 2020 Jun;83:106418. doi: 10.1016/j.intimp.2020.106418. Epub 2020 Apr 30.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized by synovial inflammation and hyperplasia resulting from an imbalance between the proliferation and apoptosis of fibroblast-like synoviocytes (FLSs). Our previous study found that sorafenib had inhibitory effects in rats with adjuvant arthritis (AA). The present study investigated the role of sorafenib in the induction of AA FLS apoptosis in vitro. FLSs obtained from AA rats were cultured in vitro and identified. Cell apoptosis was detected using terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) labeling methods. Real-time PCR and Western blotting assays were used to quantify the expression levels of Fas, Caspase-3, Mcl-1, NF-κB and C-jun gene products in AA FLSs. Our data revealed that sorafenib (4 μmol/L) induced apoptosis in AA FLSs, and flow cytometry analysis showed that AA FLSs treated with sorafenib (4 μmol/L) in vitro accumulated in early and late apoptosis. There were significant increases in the expression levels of Fas, Caspase-3 and Mcl-1, and significant decreases in NF-κB and C-jun expression in AA FLSs treated with sorafenib. In summary, these results demonstrate that sorafenib promotes AA FLS apoptosis, which may be related to the upregulation of Fas and Caspase-3 and downregulation of NF-κB and C-jun. All of these findings suggest that sorafenib exerts an inhibitory effect on AA rats in vivo via AA FLS apoptotic induction, which has potential therapeutic implications for RA.
类风湿关节炎（RA）是一种慢性自身免疫性疾病，其特征是滑膜炎症和增生，这是由于成纤维样滑膜细胞（FLS）的增殖和凋亡失衡所致。我们之前的研究发现索拉非尼对佐剂性关节炎（AA）大鼠具有抑制作用。本研究探讨了索拉非尼在体外诱导 AA FLS 凋亡中的作用。从 AA 大鼠中分离出的 FLS 在体外进行培养和鉴定。采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）和膜联蛋白 V-异硫氰酸荧光素（FITC）和碘化丙啶（PI）标记法检测细胞凋亡。实时 PCR 和 Western blot 检测用于定量 AA FLS 中 Fas、Caspase-3、Mcl-1、NF-κB 和 C-jun 基因产物的表达水平。我们的数据表明，索拉非尼（4 μmol/L）诱导 AA FLS 凋亡，流式细胞术分析表明，体外用索拉非尼（4 μmol/L）处理的 AA FLS 早期和晚期凋亡增加。用索拉非尼处理的 AA FLS 中 Fas、Caspase-3 和 Mcl-1 的表达水平显著增加，NF-κB 和 C-jun 的表达水平显著降低。总之，这些结果表明，索拉非尼促进 AA FLS 凋亡，这可能与 Fas 和 Caspase-3 的上调以及 NF-κB 和 C-jun 的下调有关。所有这些发现表明，索拉非尼通过诱导 AA FLS 凋亡对体内 AA 大鼠发挥抑制作用，这对 RA 具有潜在的治疗意义。
