三叶青黄酮对荷Lewis肺癌小鼠髓源性抑制细胞的作用  

Effect of Flavonoids from Tetrastigma Hemsleyanum Diels et Gilg on Myeloid Derived Suppressive cells in Mice Bearing Lewis Lung Cancer

作　　者：胡桃 冯正权[2] 钟良瑞[2] 梁波 HU Tao;FENG Zheng-quan;ZHONG Liang-rui;LIANG Bo(Department of Mental Health Center,Tongde Hospital of Zhejiang Province,Hangzhou 310012;Department of Oncology,Tongde Hospital of Zhejiang Province,Hangzhou 310012)

机构地区：[1]浙江省立同德医院精神卫生中心,杭州310012 [2]浙江省立同德医院肿瘤科,杭州310012

出　　处：《中国中西医结合杂志》2018年第10期1229-1233,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.81541084);浙江省自然科学基金资助项目(No.LQ15H290006);浙江省立同德医院院级项目(No.2D1503)

摘　　要：目的研究三叶青黄酮对荷Lewis肺癌小鼠髓源性抑制细胞(MDSCs)的作用,探讨三叶青黄酮抗肿瘤机制。方法 40只C57BL/6雌性小鼠随机分为5组,三叶青黄酮高(100 mg/m L)、中(50 mg/m L)、低剂量组(25 mg/m L)、造模组及正常组,每组8只。除正常组外各组小鼠建立肺癌模型,24 h后各组灌胃给药。14天后处死小鼠,剥取瘤组织,计算抑瘤率;流式细胞仪检测小鼠脾脏中MDSCs(GR-1^+CD11b^+)、CD4^+T和CD8^+T细胞的表达;酶联免疫吸附法测定小鼠外周血中一氧化氮合成酶(i NOS)和精氨酸酶1(Arg-1)表达。结果三叶青黄酮高、中、低剂量组抑瘤率分别为:44. 3%、29. 2%、15. 4%。与正常组比较,造模组MDSCs(GR-1^+CD11b^+)及Arg-1、i NOS含量及CD8^+T比例增高(P <0. 01)、CD4^+T比例、CD4^+T/CD8^+T比值降低(P <0. 01)。与造模组比较,三叶青黄酮各组MDSCs(GR-1^+CD11b^+)含量、CD8^+T细胞比例、Arg-1、i NOS含量降低,CD4^+T细胞比例、CD4^+T/CD8^+T比值升高(P <0. 01)。与三叶青黄酮高剂量组比较,三叶青黄酮中剂量及低剂量组MDSCs(GR-1^+CD11b^+)含量、CD8^+T细胞比例、Arg-1含量升高,CD4^+T细胞比例、CD4^+T/CD8^+T比值降低(P <0. 05,P <0. 01),同时三叶青黄酮低剂量组i NOS含量增高(P <0. 01)。结论三叶青黄酮可通过改善荷瘤小鼠肿瘤免疫抑制状态发挥抗肿瘤作用,其机制可能与三叶青黄酮可下调MDSCs及其相关炎症因子的表达有关。Objective To study the effects of flavonoids from Tetrastigma hemsleyanum Diels et Gilg on myeloid derived suppressive cells（ MDSCs） in mice bearing Lewis lung cancer,and to discuss antitumor activity. Methods Totally 40 C57 BL/6 female mice were divided into 5 groups randomly,including high-（ 100 mg/m L）,medium-（ 50 mg/m L） and low-dose（ 25 mg/m L） groups,model group and normal group,8 in each group. The mice were established with lung cancer,except the mice in the normal group. Gavage was conducted 24 h later according to the groups. 14 days later,mice were sacrificed to pick off tumor inhibition tissue and calculate tumor rate. Flow cytometry was used to detect the expression of MDSCs（ GR-1^＋CD11 b^＋）,CD4^＋T and CD8^＋T cells in mice spleen. Enzyme linked immunosorbent assay was used to determine expression of inducible nitric oxide synthase（ i NOS） and Arginase-1（ Arg-1）in peripheral blood of mice. Results The tumor inhibition rate of high-,medium-and low-dose group was 44. 3%,29. 2% and 15. 4% respectively. Compared with the normal group,the content of MDSCs（ GR-1^＋CD11 b^＋）,Arg-1 and i NOS and the proportion of CD8^＋T increased in the model group（ P〈0. 01）,while the proportion of CD4^＋T and CD4^＋T/CD8^＋T declined（ P〈0. 01）. Compared with the model group,the content of MDSCs（ GR-1^＋CD11 b^＋）,theproportion of CD8^＋T cells and the content of Arg-1 and i NOS declined in the high-,medium-and low-dose groups,while the proportion of CD4^＋T cells and the ratio of CD4^＋T/CD8^＋T increased（ P〈0. 01）. Compared with high-dose group,the content of MDSCs（ GR-1^＋CD11 b^＋）,the proportion of CD8^＋T cells and the content of Arg-1 increased in the medium-and low-dose groups,while the proportion of CD4^＋T cells and the ratio of CD4^＋T/CD8^＋T declined（ P〈0. 05,P0. 01）. In the meantime,the content of i NOS increased in the low-dose group（ P〈0. 01）. Conclusion The flavonoids from Tetrastigma hemsleyanum Diels et Gilg co

关 键 词：三叶青黄酮 髓系来源抑制细胞 免疫抑制 

分 类 号：R285.5[医药卫生—中药学]