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运动对 7,12-二甲基苯蒽诱导的实验性乳腺癌小鼠免疫应答细胞特征和细胞因子合成的影响。

The influence of physical activity on the profile of immune response cells and cytokine synthesis in mice with experimental breast tumors induced by 7,12-dimethylbenzanthracene.

机构信息

Department of Immunology, Federal University of the Triângulo Mineiro (UFTM), Oncology Research Institute (IPON), Uberaba, Minas Gerais, Brazil.

出版信息

Eur J Cancer Prev. 2013 May;22(3):251-8. doi: 10.1097/CEJ.0b013e3283592cbb.

DOI:10.1097/CEJ.0b013e3283592cbb
PMID:22976388
Abstract

This study aims to investigate cytokine synthesis by lymphocytes in the presence of mammary tumors and the interaction with physical activity. For this study, we used 56 female Balb/c, 8-week-old, virgin mice with a body mass between 20 and 30 g. The mice were divided into four groups: a no tumor/nontrained control group; a no tumor/trained group subjected to physical training of swimming in water (30 ± 4°C) for 45 min, five times per week for 8 weeks; a tumor/nontrained (sedentary) group in which the animals received 7,12-dimethylbenzanthracene [(DMBA) 1 mg/ml weekly for 6 weeks)]; and a tumor/trained group in which animals were subjected to the aforementioned DMBA tumor induction and swim training protocols. After the experimental period, immune cells were collected from spleen cell specimens, placed in culture, and stimulated with lipopolysaccharide. The presence of cluster of differentiation (CD)3, CD4, and CD8 markers and the expression of interferon-γ, interleukin (IL)-2, IL-4, IL-10, IL-12, transforming growth factor β, and tumor necrosis factor α cytokines were assessed by flow cytometry and enzyme-linked immunosorbent assay. Physical activity increased the quantities of lymphocytes producing interferon γ, IL-2, IL-12, and tumor necrosis factor α and decreased the quantities of lymphocytes and macrophages expressing IL-4, IL-10, and transforming growth factor β. In contrast, tumor induction, in the absence of swim training, reduced Th1 cytokine levels while increasing the presence of Th2 cytokines and Treg cells. Physical activity promoted reductions in the incidence of tumor development and promoted immune system polarization toward an antitumor Th1 response pattern profile.

摘要

本研究旨在探讨乳腺肿瘤存在时淋巴细胞的细胞因子合成及其与体力活动的相互作用。为此,我们使用了 56 只 8 周龄、体重在 20-30g 之间的雌性 Balb/c 未孕小鼠。将这些小鼠分为四组:无肿瘤/未训练对照组;无肿瘤/训练组,接受游泳训练(水温 30±4°C),每周 5 次,共 8 周;肿瘤/未训练(久坐)组,每周接受 7,12-二甲基苯蒽(DMBA)[1mg/ml]注射,共 6 周;肿瘤/训练组,动物接受上述 DMBA 肿瘤诱导和游泳训练方案。实验结束后,从脾细胞标本中收集免疫细胞,置于培养物中,用脂多糖刺激。通过流式细胞术和酶联免疫吸附试验评估分化群(CD)3、CD4 和 CD8 标志物的存在以及干扰素-γ、白细胞介素(IL)-2、IL-4、IL-10、IL-12、转化生长因子-β和肿瘤坏死因子-α细胞因子的表达。体力活动增加了产生干扰素 γ、IL-2、IL-12 和肿瘤坏死因子-α的淋巴细胞数量,并减少了表达 IL-4、IL-10 和转化生长因子-β的淋巴细胞和巨噬细胞数量。相反,在没有游泳训练的情况下,肿瘤诱导降低了 Th1 细胞因子水平,同时增加了 Th2 细胞因子和 Treg 细胞的存在。体力活动促进了肿瘤发生的减少,并促进了免疫系统向抗肿瘤 Th1 反应模式的极化。

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