羧胺三唑抑制佐剂性关节炎大鼠腹腔巨噬细胞产生细胞因子  

Inhibitory effects of carboxyamidotriazole on cytokines production by peritoneal macrophages from adjuvant arthritis rats

作　　者：朱蕾[1] 段梦园 张晓娟[1] 李娟[1] 鞠瑞[1] 郭磊[1] 卢珊[1] 叶菜英[1] ZHU Lei;DUAN Meng-yuan;ZHANG Xiao-juan;LI Juan;JU Rui;GUO Lei;LU Shan;YE Cai-ying(Dept. of Pharmacology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China)

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院基础学院药理系,北京100005

出　　处：《基础医学与临床》2018年第6期798-802,共5页Basic and Clinical Medicine

基　　金：中国医学科学院医学与健康科技创新工程(2016-I2M-1-002);"重大新药创制"科技重大专项(2014ZX09507003-003);国家自然科学基金(81102454);中国医学科学院医学表观中心基金(2017PT31035)

摘　　要：目的探讨羧胺三唑(CAI)体外对佐剂性关节炎(AA)大鼠腹腔巨噬细胞产生细胞因子的影响。方法采用弗氏完全佐剂诱导大鼠AA模型,无菌制备大鼠腹腔巨噬细胞,加CAI(10、20和40μmol/L)体外培养;ELISA法检测细胞培养上清中TNF-α、IL-1β和IL-6含量;荧光定量PCR法检测细胞内TNF-α、IL-1β和IL-6的mRNA表达;Trans AM试剂盒检测核蛋白NF-κB p65的DNA结合活性。结果 CAI(20、40μmol/L)能够明显降低AA大鼠腹腔巨噬细胞培养上清中TNF-α、IL-1β和IL-6水平,减少细胞内TNF-α、IL-1β和IL-6的mRNA表达,同时也能够抑制核内NF-κB p65的DNA结合活性(P<0.05,P<0.01)。结论 CAI可能通过抑制NF-κB的活性而减少AA大鼠腹腔巨噬细胞内TNF-α、IL-1β和IL-6等促炎细胞因子的产生,CAI的抗关节炎作用可能与上述机制有关。Objective To explore the effects of carboxyamidotriazole（ CAI） on cytokines production by peritoneal macrophages from adjuvant arthritis（ AA） rats in vitro. Methods Freund＇s completed adjuvant was used to induce AA in rats. Peritoneal macrophages were prepared from asepsis and incubated with CAI（ 10,20,40 μmol/L）. The contents of TNF-α,IL-1β and IL-6 in the culture supernatant were measured by ELISA,and mRNA expressions of TNF-α,IL-1β and IL-6 were determined by real-time quantitative PCR. NF-κB p65 DNA binding activity in the nuclear protein was detected with Trans AM kit. Results The level of TNF-α,IL-1β and IL-6 in the culture supernatant,their intracellular mRNA expression and NF-κB p65 DNA-binding activity in peritoneal macrophages of AA rats were significantly inhibited by CAI（ 20 and 40 μmol/L）（ P〈0. 05 and P〈0. 01）.Conclusions CAI may decrease the production of pro-inflammatory cytokines such as TNF-α,IL-1β and IL-6 through inhibiting the activation of NF-κB,which is potentially associated with its anti-arthritic mechanisms.

关 键 词：羧胺三唑 佐剂性关节炎 巨噬细胞 细胞因子 核因子-ΚB 

分 类 号：R96[医药卫生—药理学]