>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
胸腺五肽对肺癌模型小鼠免疫功能及脾脏TLR4信号通路的作用
作者:王雪海  李钢  罗青松  谢家勇  甘崇志 
单位:四川省医学科学院·四川省人民医院 胸外科, 四川 成都 610072
关键词:胸腺五肽 肺癌 小鼠 免疫功能 Toll样受体-4信号通路 
分类号:R734.2;R-33
出版年·卷·期(页码):2019·38·第三期(466-470)
摘要:

目的:研究胸腺五肽对肺癌模型小鼠免疫功能及脾脏Toll样受体-4(TLR-4)信号通路的作用。方法:40只C57BL/6小鼠随机分为正常对照组、模型对照组、环磷酰胺组和胸腺五肽组,除正常对照组外其他3组小鼠制作肺癌模型。造模成功后各组小鼠治疗2周,然后测定血液调节性T细胞(Treg细胞)和辅助性T细胞17(Th17细胞)水平及脾脏组织中TLR4、肿瘤坏死因子受体相关因子-6(TRAF-6)、核因子-κB(NF-κB)、激活蛋白-1(AP-1) mRNA和蛋白表达。结果:(1)胸腺五肽组小鼠血液Treg细胞和Th17细胞水平显著高于环磷酰胺组(P<0.01),而Treg细胞/Th17细胞值显著低于模型对照组(P<0.01);(2)胸腺五肽组小鼠脾脏TLR4、TRAF-6、NF-κB、AP-1 mRNA和蛋白表达水平显著低于环磷酰胺组(P<0.01)。结论:肺癌小鼠接受环磷酰胺化疗时辅以胸腺五肽治疗可调节其免疫功能,下调脾脏TLR4信号通路TLR4、TRAF-6、NF-κB及AP-1的表达。

Objective:To study the effect of thymopentin on the immunologic function and Toll like recptor-4(TLR-4) signal pathway in the spleen in mouse model of lung cancer. Methods:Forty mice of C57BL/6 were randomly divided into normal control(NC) group, model control(MC) group, cyclophosphamide(CPM) group and thymopentin(THY) group. Except NC group, mice in other three groups were given subcutaneously Lewis lung cancer cells under right armpit to make mouse model of lung cancer. After two-week treatment, regulatory T cell(Treg cell) and T help cell 17(Th17 cells) were determined, and mRNA and protein of TLR4, tumor necrosis factor receptor-associated factor-6(TRAF-6), nuclear factor-κB (NF-κB) and activating protein-1(AP-1) were determined by transcription-polymerase chain reaction and Western-blotting. Results:(1)Compared with CPM group, the level of Treg and Th17 cells in THY group were increased significantly(P<0.01), and the ratio of Treg/Th17 was decreased significantly(P<0.01). (2)Compared with CPM group, the mRNA and protein level of TLR4, TRAF-6, NF-κB and AP-1 in the spleen of THY group were decreased significantly(P<0.01). Conclusion:Adjuvant therapy of thymopentin in the chemotherapy of cyclophosphamide for the mice with lung cancer can regulate the immunologic function and down-regulate the level of TLR4, TRAF-6, NF-κB and AP-1 in the TLR4 signal pathway in the spleen.

参考文献:

[1] WOO S R,FUETES M B,CORRALES L,et al.STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors[J].Immunity,2014,41(5):830-842.
[2] LING L,ZHAO P,YAN G,et al.The frequency of Th17 and Th22 cells in patients with colorectal cancer at pre-operation and post operation[J].Immunol Invest,2015,44(1):56-59.
[3] 邵素芳,于春美.卵巢癌患者外周血Th17/Treg细胞的检测及其临床意义[J].山东医药,2015,55(15):37-39.
[4] 于莉莉,韩代书.Toll样受体(TLR)介导的天然免疫间的相互调节[J].中国组织化学与细胞化学杂志,2013,21(1):79-84.
[5] GARLANDA C,RIVA F,BONAVITA E,et al.The decoys and regulatory receptors of the IL-1/toll-like receptor superfamily[J].Front Immunol,2013,9(4):180-181.
[6] 郭尚函,林炎龙,赵仓焕,等.耳穴贴压对睡眠剥夺大鼠脾脏TLR4信号通路关键基因mRNA表达的影响[J].暨南大学学报(自然科学与医学版),2015,36(4):313-318.
[7] MEL B,EW J,KA H,et al.Disruption of a new forkhead/winged-helix protein,scurfin,results in the fatal lymphoproliferative disorder of the scurfy mouse[J].Nat Genet,2011,27(1):68-73.
[8] ZHAO J X,ZENG Y Y,LIU Y.Fetal alloantigen is responsible for the expansion of the CD4(+)CD25(+) Regulatory T cell pool during pregnancy[J].J Reprod Immunol,2007,75(2):71-81.
[9] DR L,AY R.Th17 and regulatory T cells in mediating and restraining inflammation[J].Cell,2010,146(6):845-858.
[10] SHIMON S,TOMOYUKI Y,TAKASHI N,et al.Regulatory T cells and immune tolerance[J].Cell,2008,133(5):775-787.
[11] SCHMAUSSER B,ANDRULIS M,ENDRICH S,et al.The Toll-like receptors TLR4,living and TLR9 on gastric carcinoma cells:an implication For interaction with Helicobacter pylori[J]. J Med Microbiol,2005,295(3):179-185.
[12] INOUE J,GOHDA J,AKIYAMA T,et al.The NF-kappa B activation in development and progression of cancer[J].Cancer Sci,2007,98(3):268-274.
[13] ZHANG Y B,HE F L,FANG M,et al.The Increased expression of Toll like 4 and 9 receptors in the human lung cancer[J].J Mol Biol Rep,2009,4(6):1475-1481.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 237989 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364