甘草总黄酮及其成分异甘草素调控M2型巨噬细胞极化的机制研究  

Total flavonoid from Glycyrrhizae Radix et Rhizoma and its ingredient isoliquiritigenin regulation M2 phenotype polarization of macrophages

作　　者：王原来[1] 谭希[1] 杨晓露 李晓芸[1] 卞卡[1,3] 章丹丹[1] 

机构地区：[1]上海中医药大学穆拉德中药现代化研究中心,上海201203 [2]上海市宝山区中西医结合医院药剂科,上海201999 [3]美国乔治华盛顿大学生物化学与分子生物学系,华盛顿20052

出　　处：《中国中药杂志》2015年第22期4475-4481,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81573673);国家自然科学基金青年项目(81001666);上海市教育委员会科研创新项目(13YZ048);上海高校选拔培养优秀青年教师基金项目(SZY07029);上海市卫生和计划生育委员会科研课题项目(20144Y0143)

摘　　要：考察甘草总黄酮(TFRG)及异甘草素(ISL)对M2型巨噬细胞的调控机制。利用IL-4(60μg·L-1)诱导鼠源RAW264.7巨噬细胞6 h为M2型巨噬细胞。TFRG及ISL在Trans-well小室迁移实验中减弱因M2型巨噬细胞导致乳腺癌4T1细胞的体外迁移力提高。TFRG和ISL呈剂量依赖性抑制精氨酸酶1(Arg-1)在基因和蛋白水平的表达,并提高血红素加氧酶1(HO-1)的基因表达,同时提高诱导型一氧化氮合酶(i NOS)的蛋白表达,提高microRNA-155及其靶基因之一SHIP1的表达,并降低信号转导及转录活化因子3和6(STAT3/6)蛋白磷酸化水平。TFRG及其成分ISL是甘草抑制巨噬细胞向M2表型极化的活性组分和成分,部分通过调控miR155和STAT信号通路,影响Arg-1等M2型特征物的表达而抑制巨噬细胞M2表型极化后提高的乳腺癌细胞体外迁移力。To study the mechanisms of total flavonoid from Glycyrrhizae Radix et Rhizoma （TFGR） and its ingredient isoliquiritige- nin（ISL） on their regulation of M2 phenotype polarization of macrophages. IL-4 （60 μg·L-1） induced RAW264. 7 cells for 6 h to establish the M2 macrophage model. TFGR and ISL restrained breast cancer cells migration with the aid of M2 macrophages in vitro. TFGR and ISL in- hibited gene and protein expression of Arg-1, up-regnlated gene of HO-1 and protein expression of iNOS, enhanced the expression of microR- NA 155 and its target gene SHIP1, meanwhile down-regulated the phosphorylation of STAT3 and STAT6. So TFGR and ISL were the bioactive fraction and ingredient in Glycyrrhizae Radix et Rhizoma to reverse M2 phenotype macrophages polarization. TFGR and ISL inhibited the promotion of M2 macrophages to breast cancer cells migration in vitro, STAT signal pathways and miR155 were partly involved.

关 键 词：甘草总黄酮 异甘草素 巨噬细胞 表型极化 作用机制 

分 类 号：R285.5[医药卫生—中药学]