Apoptosis effects of imperatorin on synoviocytes in rheumatoid arthritis through mitochondrial/caspase-mediated pathways
Apoptosis effects of imperatorin on synoviocytes in rheumatoid arthritis through mitochondrial/caspase-mediated pathways
复制标题
欧前胡素通过线粒体/半胱天冬酶介导的途径对类风湿性关节炎滑膜细胞凋亡的影响
DOI：
10.1039/c7fo01748k
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发表时间：
2018-04-01
期刊：
影响因子：
6.1
通讯作者：
Wei, Zhao-jun
中科院分区：
文献类型：
--
作者：
Zhai, Ke-feng;Duan, Hong;Wei, Zhao-jun
类风湿关节炎(RA)是一种全身性慢性炎症性疾病，与类风湿关节炎成纤维细胞样滑膜细胞(RA-FLSS)的生长和死亡之间的潜在失衡有关。香豆素(IPT)是一种天然存在的呋喃香豆素，存在于伞形科蔬菜、柑橘类水果和一些草本植物中。IPT对RA-Fls增殖和凋亡的影响及其可能的机制尚不清楚。用白细胞介素1β(IL-1β)诱导RA患者RA-FLSS，并用IPT治疗。用四甲基偶氮唑盐比色法测定细胞存活率。Annexin V-FITC/PI双染和Hoechst 33342染色分析细胞凋亡。用荧光显微镜观察线粒体膜电位(Delta Psi(M))的改变，用免疫印迹法检测线粒体膜电位的变化，用免疫印迹法检测线粒体膜电位的变化，而对雄性Wistar大鼠进行体内研究，然后用TUNEL法和HE染色进行组织病理学评价。结果表明，IPT可显著降低IL-1β诱导的RA-FLSS的细胞存活率，促进细胞凋亡，降低基质金属蛋白酶-1/-3的表达。此外，与IL-1β诱导的治疗相比，IPT暴露被发现扰乱了Delta Psi(M)。此外，IPT还可增加线粒体细胞色素C的释放、Bax/Bcl2的比值以及caspase-9、caspase-3和聚(ADP-核糖)聚合酶的裂解。体内研究表明，IPT不仅通过减少滑膜增生和血管疙瘩的形成而显著减轻胶原性关节炎，而且还能提高踝关节细胞的凋亡指数。综上所述，我们的研究结果提示IPT抑制RA-Fls的细胞增殖并诱导其凋亡，这可能与线粒体/caspase介导的信号通路有关。
Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease associated with a potential imbalance between the growth and death of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Imperatorin (IPT) is a naturally occurring furanocoumarin found in umbelliferous vegetables, citrus fruits, and some herbs. The effects of IPT on the proliferation and apoptosis of RA-FLSs and its potential underlying mechanisms have remained unclear. RA-FLSs obtained from RA patients were induced by interleukin-1 beta (IL-1 beta) and treated with IPT. Cell viability was determined by MTT assay. Apoptotic cell death was analyzed by Annexin V-FITC/PI double staining and Hoechst 33342 staining. The loss in the mitochondrial membrane potential (Delta Psi(m)) was visualized on the basis of JC-1 staining via fluorescence microscopy, and protein expression changes were assessed by western blot, whereas in vivo studies were conducted in male Wistar rats followed by histopathological assessment via TUNEL assay and HE staining of tissues. The results showed that IPT significantly reduced cell viability, accelerated cell apoptosis and decreased matrix metalloproteinases-1/-3 expression in IL-1 beta-induced RA-FLSs. Furthermore, IPT exposure was found to disrupt the Delta Psi(m) compared to the IL-1 beta-induced treatment. Moreover, IPT increased the release of mitochondrial cytochrome C, the ratio of Bax/Bcl-2, and the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In vivo studies showed that IPT not only significantly reduced the collagen induced arthritis by reducing synovial hyperplasia, and pannus formation but also enhanced the apoptotic index of ankle joint cells. Conclusively, our findings suggest that IPT inhibits cell proliferation and induces apoptosis in RA-FLSs that may be associated with mitochondrial/caspase-mediated signalling pathways.