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

作　　者：白永峰 曹乌吉斯古楞 BAI Yongfeng;CAO Wujisiguleng(Mongolian Medicine Research and Development Engineering Key Laboratory of the Ministry of Education,Inner Mongolia Minzu University,Tongliao 028000,China;Key Laboratory of Ethnic Medicine,Ministry of Education,Minzu University of China,Beijing 100081,China;College of Pharmacy,Naval Medical University,Shanghai 200433,China)

机构地区：[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]中央民族大学民族医药教育部重点实验室,北京100081 [3]中国人民解放军海军军医大学药学院,上海200433

出　　处：《中华中医药杂志》2024年第7期3680-3684,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家重点研发计划中医药现代化研究重点专项(No.2019YFC1712303);内蒙古自然科学基金项目(No.2020MS08025);内蒙古高等学校科学技术研究项目(No.NJZZ20108);中国博士后科学基金项目(No.2017M613340);中央民族大学民族医药教育部重点实验室开放课题(No.KLEM-KF2019Y02)。

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-κB 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150μmol/L、马钱苷酸为150μmol/L、獐牙菜苦苷为30μmol/L、獐牙菜苷为150μmol/L、异荭草素为200μmol/L、异牡荆素为200μmol/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。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 150μmol/L,loganic acid was 150μmol/L,swertiamarin was 30μmol/L,sweroside was 150μmol/L,isoorientin was 200μmol/L,isovitexin was 200μmol/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-xB 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 

分 类 号：R285[医药卫生—中药学]