大黄素甲醚通过影响AKT信号通路抑制LPS诱导人巨噬细胞的炎症反应  

Study on effect of physcion on inflammatory mediators by influencing the AKT signaling pathway in stimulated macrophage

作　　者：刘钊[1] 杨鸿[1] 李雪丽[1] LIU Zhao;YANG Hong;LI Xue-li(Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases,Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院医学实验中心,北京市中医药防治重大疾病基础研究重点实验室,北京100700

出　　处：《时珍国医国药》2021年第3期566-569,共4页Lishizhen Medicine and Materia Medica Research

基　　金：中国中医科学院自主选题项目(ZZ2015008,ZZ2016004)。

摘　　要：目的研究大黄素甲醚抑制免疫细胞炎症反应的作用及可能机制。方法采用脂多糖(lipopolysaccharide, LPS)刺激人急性单核白血病细胞(human acute monocytic leukemia cell line, THP-1)制备免疫细胞炎症模型,应用液相蛋白芯片技术检测了大黄素甲醚对LPS诱导的THP-1细胞分泌炎症因子的作用及对蛋白激酶B(protein kinase B,AKT)信号通路关键蛋白表达的影响。结果大黄素甲醚低中高药物组(0.280,0.560和1.125μmol/L)能够通过下调丝裂原活化蛋白激酶激酶1蛋白的表达和磷酸化蛋白激酶B、磷酸化丝裂原活化蛋白激酶激酶1蛋白、磷酸化细胞Jun蛋白、磷酸化细胞外调节蛋白激酶1/2及磷酸化雷帕霉素受体蛋白的磷酸化水平(P<0.05,P<0.01),抑制LPS诱导的THP-1细胞释放白介素(interleukin^(-1)β,IL^(-1)β)类分子IL^(-1)β、IL-2、IL-4、IL-6、IL-8、IL^(-1)2(p70)、IL^(-1)7、粒细胞集落刺激因子、粒细胞-巨噬细胞集落刺激因子、γ-干扰素和肿瘤坏死因子-α(P<0.05,P<0.01)。结论现有数据表明大黄素甲醚对LPS诱导的THP-1细胞的炎症反应有一定的抑制作用,其作用机制可能与抑制AKT信号通路的激活有关。Objective To investigate the effect and possible mechanism of physcion on the inflammation response of immune cells.Methods LPS stimulated human acute mononuclear leukemia cell line(THP-1) has been used as inflammatory experimental model.The anti-inflammatory effect of physcion on the expression of cytokines and protein kinase B(protein kinase B, AKT) signal pathway of THP-1 cell secretion induced by LPS was detected by liquichip technique.Results The low, medium and high dosage groups(0.280,0.560 and 1.125 μmol/L)of physcion was able to repress mitogen-activated protein kinase1 expression and protein kinase B, MEK1, cell-Jun, extracellular regulatory protein kinase 1/2, mammalian target of rapamycin phosphorylation(P<0.05,P<0.01),while resist LPS-induced THP-1 cells expressing IL^(-1)β,IL-2,IL-4,IL-6,IL-8,IL^(-1)2(P70),IL^(-1)7,granulocyte colony factor, granulocyte-macrophage colony stimulus factor, Interferon-γ and tumor necrosis factor-α(P<0.05,P<0.01).Conclusion The data presented here suggested that the physcion has inhibitory effects on the LPS-induced inflammation of THP-1 cells, and its mechanism may be related to the inhibition of AKT signaling pathways.

关 键 词：大黄素甲醚 细胞因子 信号通路 炎症 

分 类 号：R285.5[医药卫生—中药学]