A771726体外给药对LPS刺激的胶原性关节炎大鼠腹腔巨噬细胞免疫功能的影响  

Effects of the active metabolite of leflunomide,A771726,on the immune function of LPS-stimulated peritoneal macrophages from collagen-induced arthritis rats in vitro

作　　者：王小华[1] 李俊[1] 王婷玉[1] 周倩[1] 

机构地区：[1]安徽医科大学药学院,合肥230032

出　　处：《安徽医科大学学报》2009年第3期362-365,共4页Acta Universitatis Medicinalis Anhui

基　　金：高等学校博士学科专项科研基金(编号:20050366003)

摘　　要：目的研究来氟米特活性代谢产物A771726对LPS刺激的胶原性关节炎(CIA)大鼠腹腔巨噬细胞(PMФ)免疫功能的影响及其可能的机制。方法应用鸡Ⅱ型胶原(CⅡ)建立大鼠CIA模型,无菌制备CIA大鼠PMФ悬液,A771726(0.1、1、10μmol/L)体外用药,小鼠胸腺细胞增殖法测定CIA大鼠PMФ分泌白细胞介素1(IL-1)的水平;化学法检测A771726对CIA大鼠PMФ氧化应激的影响;逆转录-聚合酶链反应(RT-PCR)法检测A771726对CIA大鼠PMФ中TLR4 mRNA表达的影响。结果A771726(1、10μmol/L)体外用药,可有效降低CIA大鼠PMФ的分泌功能;显著改善CIA大鼠PMФ的氧化应激状态;RT-PCR结果表明,A771726(1、10μmol/L)体外用药可显著降低CIA大鼠PMФ中TLR4 mRNA的表达。结论A771726(1、10μmol/L)能调节LPS刺激的CIA大鼠PMФ分泌功能与氧化应激,其机制是否与A771726抑制CIA大鼠PMФ中TLR4 mRNA的表达水平有关值得进一步探讨。Objective To investigate the effect of A771726 on the immune function of peritoneal macrophages （PMФ） in collagen-induced arthritis （CIA） and its potential mechanism. Methods Chicken type Ⅱ collagen （C Ⅱ） was used to induce CIA in rats. Peritoneal macrophages suspensions of CIA rats were prepared in asepsis and incubated with A771726 （0. 1,1,10 μmol/L） in vitro. Interleukin-1 （IL-1） was measured by mouse thymoeyte proliferation assay. Oxidative stress was assessed by chemical methods. The expression of TLR4 mRNA of PMФ in CIA rats were detected by reverse transcription polymerase chain reaction（RT-PCR） analysis. Results A771726 （1,10 μmol/L）significantly inhibited the secretion function of PMФ in CIA rats. A771726 （1,10 μmol/L） markedly ameliorate oxidative stress in PMФ of CIA rats. In addition, A771726 （ 1,10 μmol/L） significantly inhibited the expression of TLR4 mRNA of PMФ in CIA rats. Conclusion A771726 （ 1,10 μmol/L） can regulate the secretion function and oxidative stress, and advanced investigation. Iits mechanism whether or not be related to inhibitory level of TLR4mRNA of PMФ in CIA rats would be performed in future.

关 键 词：异[口恶]唑类/药理学 关节炎 实验性 巨噬细胞 腹 

分 类 号：R341.32[医药卫生—基础医学] R684.3