麻花艽6个成分对类风湿性关节炎滑膜成纤维样细胞的影响及机制
Effects and its mechanism of six components of Gentiana straminea Maxim.in rheumatoid arthritis fibroblast-like synoviocytes
白永峰 1曹乌吉斯古楞2
作者信息
- 1. 内蒙古民族大学蒙医药研发工程教育部重点实验室,通辽 028000
- 2. 内蒙古民族大学蒙医药研发工程教育部重点实验室,通辽 028000;中央民族大学民族医药教育部重点实验室,北京 100081;中国人民解放军海军军医大学药学院,上海 200433
- 折叠
摘要
目的:探讨麻花艽6个成分对类风湿性关节炎滑膜成纤维样细胞(RA-FLS)的影响及机制.方法:采用CCK-8法筛选麻花艽6个成分的最佳给药浓度;流式细胞术测定最佳给药浓度干预下的细胞凋亡水平,ELISA检测细胞凋亡诱导因子(AIF)及基质金属蛋白酶(MMPs)表达水平;Western Blot法检测沉默信息调节因子1(SIRT1)、核因子-κB p65(NF-KB p65)、Bcl-2、Bax蛋白表达情况.结果:麻花艽6个成分最佳给药浓度:龙胆苦苷为150 μmol/L、马钱苷酸为150 μmol/L、獐牙菜苦苷为30 μmol/L、獐牙菜苷为150 μmol/L、异荭草素为200 μmol/L、异牡荆素为200 μ mol/L.与空白对照组比较,龙胆苦苷的促细胞凋亡作用最强(P＜0.01),马钱苷酸、獐牙菜苦苷、异荭草素次之(P＜0.01),獐牙菜苷、异牡荆素组最次(P＜0.05);各给药组能显著增加RA-FLS中AIF表达(P＜0.01,P＜0.05),显著降低RA-FLS中MMPs表达(P＜0.01,P＜0.05);各给药组能显著降低RA-FLS中NF-κB p65、Bcl-2蛋白表达(P＜0.05),显著增加SIRT1、Bax蛋白表达(P＜0.05).结论:麻花艽6个成分具有一定的抑制RA-FLS增殖活性和促凋亡作用,并能调控AIF和MMPs的表达,其潜在机制可能是通过抑制NF-κB信号通路炎症因子的释放和促进线粒体凋亡通路中诱导凋亡因子、促凋亡蛋白水平来促进RA-FLS凋亡.
Abstract
Objective:To investigate the effects and mechanism of six components of Gentiana straminea Maxim.on rheumatoid arthritis fibroblast-like synoviocytes(RA-FLS).Methods:The optimal concentrations of Gentiana straminea Maxim.were selected by CCK-8 method.Flow cytometry(FCM)was used to determine the expression levels of pro-inflammatory factors AIF and MMPs were detected by ELISA.The expressions of SIRT1,NF-κB p65,Bcl-2 and Bax were detected by Western Blot.Results:Optimal concentrations of six components of Gentiana straminea Maxim.:gentimacroside was 150 μmol/L,loganic acid was 150 μmol/L,swertiamarin was 30 μmol/L,sweroside was 150 μmol/L,isoorientin was 200 μmol/L,isovitexin was 200 μmol/L.Compared with the blank control group,the apoptotic effect of gentimacroside was the strongest(P＜0.01),followed by loganic acid,swertiamarin,isoorientin(P＜0.01),sweroside and isovitexin were the weakest(P＜0.05),all the treatment groups significantly increased the expression of AIF(P＜0.01,P＜0.05),and significantly decreased the expression of MMPs in RA-FLS(P＜0.01,P＜0.05),all the treatment groups could significantly reduce the expression of NF-κB p65 and Bcl-2(P＜0.05)and increase the expression of SIRT1 and Bax(P＜0.05).Conclusion:The six components of Gentiana straminea Maxim.can inhibit the proliferation activity of RA-FLS and promote apoptosis,and regulate the expression of AIF and MMPs.The potential mechanism may be to promote the apoptosis of RA-FLS by inhibiting the release of inflammatory factors in NF-κB signaling pathway and promoting the levels of apoptosis-inducing factors and pro-apoptotic proteins in mitochondrial apoptosis pathway.
关键词
类风湿性关节炎/滑膜成纤维细胞/麻花艽/机制/化学成分/核因子-κB信号通路/线粒体凋亡通路Key words
Rheumatoid arthritis(RA)/Synovial fibroblasts/Gentiana straminea Maxim./Mechanism/Chemical components/NF-κB signaling pathway/Mitochondrial apoptosis pathway引用本文复制引用
基金项目
国家重点研发计划中医药现代化研究重点专项(2019YFC1712303)
内蒙古自然科学基金项目(2020MS08025)
内蒙古高等学校科学技术研究项目(NJZZ20108)
中国博士后科学基金项目(2017M613340)
中央民族大学民族医药教育部重点实验室开放课题(KLEM-KF2019Y02)
出版年
2024
国家科技期刊平台
NSTL
万方数据