二氢青蒿素通过Akt信号途径诱导类风湿关节炎滑膜细胞凋亡

Antiapoptotic effect of dihydroartemisinin on rheumatoid arthritis synoviocyte mediated by akt signaling pathway

目的探讨二氢青蒿素诱导类风湿关节炎滑膜细胞凋亡的信号机制。方法无菌条件取类风湿关节炎患者膝关节滑膜组织，组织块贴壁法培养关节滑膜细胞。流式细胞仪检测细胞凋亡。Westernblot半定量分析Akt活化。电泳迁移率变动（EM—SA）检测NF—κB活性。结果在2．5～10μmol／L质量浓度范围二氢青蒿素呈剂量依赖性诱导体外培养的关节炎滑膜细胞凋亡。5μmol／L和10μmoL／L的二氢青蒿素与关节滑膜细胞共培养24h显著抑制Akt激酶473位丝氨酸磷酸化及NF—κB的活化。结论二氢青蒿素通过Akt信号途径诱导类风湿关节炎滑膜细胞凋亡。

Objective To explore the mechanism of apoptosis in rheumatoid arthritis synoviocyte induced by dihydroartemisinin. Methods Synovial tissues were cut from rheumatoid arthritis patients when who was under knee prosthesis. Apoptosis was detected with flow cytometry. Western blot was performed to assess ser473-phosphorylated Akt. EMSA （electrophoretic mobility shift assay） was used to analyze NF-κB activation. Results Dihydroartemisin can induce apoptosis in rheumatoid arthritis synoviocyte in a dose-dependent manor from 2. 5μ mol/L to 10μmol/L. Rheumatoid Arthritis synoviocyte cultured with dihydroartemisinin in 5μmol/L or 10μmol/L can significantly inhibit serine 473 phosphorylation in Akt and activation of NF-κB. Conclusion Dihydroartemisinin can induce apoptosis in rheumatoid arthritis synoviocyte through Akt signal pathway.