干酪乳杆菌对二甲基苯蒽诱发大鼠乳腺肿瘤的抑制作用及其免疫学机制

doi:10.3969/j.issn.1004-616x.2017.01.002

癌变·畸变·突变 ›› 2017, Vol. 29 ›› Issue (1): 7-12.doi: 10.3969/j.issn.1004-616x.2017.01.002

干酪乳杆菌对二甲基苯蒽诱发大鼠乳腺肿瘤的抑制作用及其免疫学机制

梁争艳¹, 刘颖², 薛美兰², 刘佳³, 梁惠¹

1. 青岛大学公共卫生学院, 山东青岛 266021;
2. 青岛大学基础医学院, 山东青岛 266071;
3. 青岛大学药学院, 山东青岛 266021

收稿日期:2016-08-08 修回日期:2016-09-28 出版日期:2017-01-31 发布日期:2017-01-31
通讯作者: 梁惠,E-mail:qdlianghui@126.com E-mail:qdlianghui@126.com
作者简介:梁争艳,E-mail:1152381163@qq.com
基金资助:
国家自然科学基金项目（81573137）；达能营养中心膳食营养研究与宣教基金（DIC2014-03）

Inhibitory effect and immunological mechanism of Lactobacillus casei on induction of breast cancer by 7, 12-dimethylbenz (a)anthracene in rats

LIANG Zhengyan¹, LIU Ying², XUE Meilan², LIU Jia³, LIANG Hui¹

1. College of Public Health, Qingdao University, Qingdao 266021;
2. College of Basic Medicine, Qingdao University, Qingdao 266071;
3. College of Pharmacy, Qingdao University, Qingdao 266021, Shandong, China

Received:2016-08-08 Revised:2016-09-28 Online:2017-01-31 Published:2017-01-31

摘要/Abstract

摘要：

目的：探讨干酪乳杆菌对二甲基苯蒽（DMBA）诱发的大鼠乳腺肿瘤的抑制效果和对免疫功能的影响。方法：雌性SD大鼠按体质量随机分为正常对照组、模型组、低剂量和高剂量干酪乳杆菌干预组。模型组及低、高剂量干酪乳杆菌干预组大鼠右侧臀部皮下一次性注射100 mg/kg DMBA建立乳腺癌模型。低和高剂量干酪乳杆菌干预组分别灌胃给予4和8 mL/（kg·d）干酪乳杆菌（1×10⁸ CFU/mL），正常对照组和模型组均给予5 mL/（kg·d）大豆油灌胃。每天1次，持续16周后处死大鼠，完整剥离肿瘤组织及脏器，计算各组大鼠乳腺癌发生率、抑瘤率及脏器指数。流式细胞术检测大鼠外周血中自然杀伤细胞（NK）活性和T淋巴细胞亚群分布。酶联免疫吸附实验（ELISA）检测血清中细胞因子IL-4、IL-6、IL-10、IL-12、IFN-γ和TNF-α水平。结果：正常对照组大鼠无肿瘤发生，模型组、低剂量和高剂量干酪乳杆菌干预组均有肿瘤发生。与模型组比较，高剂量干酪乳杆菌组大鼠肿瘤潜伏期延长，肿瘤发生率和平均瘤质量降低（P均 < 0.05）；抑瘤率达到41.2%；且该组胸腺指数显著升高（P < 0.05）；TCRαβ⁺CD161a⁺NK细胞百分比、CD3⁺CD8⁺T细胞百分比均显著升高（P均 < 0.05）；血中CD3⁺Foxp3⁺细胞百分比明显下降（P < 0.05）。ELISA结果显示，与正常对照组比较，模型组血清中IL-4水平明显降低，而IL-6、IL-12和TNF-α水平显著升高（P均 < 0.05）；与模型组比较，高剂量干酪乳杆菌干预组，血清IL-4、IL-10浓度显著增高，IL-6、IL-12浓度显著降低（P均 < 0.05）；低和高剂量干酪乳杆菌干预组血清中TNF-α浓度均显著下降（P均 < 0.05）。结论：干酪乳杆菌对乳腺癌大鼠肿瘤生长具有一定抑制作用，其作用机制可能与干酪乳杆菌调节CD4⁺、CD8⁺T细胞、NK细胞及调节性T细胞等免疫细胞分布，改善炎性相关细胞因子水平，从而提高机体免疫调节作用有关。

关键词: 乳腺癌, 干酪乳杆菌, 免疫调节, 抗肿瘤

Abstract:

OBJECTIVE: To investigate the effect of Lactobacillus casei on 7,12-dimethylbenz(a)anthracene (DMBA) induction of breast cancer in rats. METHODS: Female Spraque-Dawley rats were randomly divided into control group (C),model group (M),low dose group of Lactobacillus casei (L1) and high dose group of Lactobacillus casei (L2). The rats were subcutaneously injected with 100 mg/kg DMBA to establish breast cancer rat model. 4 and 8 mL/kg Lactobacillus casei were administered to L1 and L2 by gavage,respectively,1 time/day,for 16 weeks in total. The latency of breast cancer in rats and Lactobacillus casei's tumor suppression rate were determined. The percentages of T lymphocytes and natural killer cells were quantified in peripheral blood of rat by flow cytometry. In addition,thymus index,spleen index and the level of interleukin 4(IL-4),IL-6,IL-10,IL-12,interferon γ (IFN-γ),and tumor necrosis factor α (TNF-α) in serum were evaluated. RESULTS: No tumor was detected in group C,whereas tumors were formed in the remaining three groups. Compared with the model group,the L2 group had extended latency of tumors,reduced tumor incidence and tumor weights (P < 0.05). In addition,the tumor inhibition rate in the same group reached 41.2%,the thymus index was increased significantly (P < 0.05),the percentage of TCRαβ⁺ CD161a⁺ NK cells and the CD3⁺CD8⁺ T cells were both increased significantly (P < 0.05),while the proportion of CD3⁺Foxp3⁺ T cells was decreased significantly (P < 0.05). ELISA results showed that,compared with the control group,the concentration of IL-4 was decreased in the model group while the concentrations of IL-6,IL-12 and TNF-α were increased (P < 0.05). In the L2 group,the concentration of IL-4 and IL-10 were significantly higher than those in the model group while the concentrations of IL-6 and IL-12 were decreased respectively (P < 0.05). In the L1 and L2 groups,TNF-α concentrations were decreased significantly compared with the model group (P < 0.05). CONCLUSION: Lactobacillus casei supplementation can inhibit the induction of tumors by DMBA in rats. A possible mechanism may involve immune-regulatory effects on the breast cancer rat model via improving the levels of inflammation-associated cytokines and changing the distribution of CD3⁺CD4⁺,CD3⁺CD8⁺ T cells,NK cells and regulatory T cells.

Key words: breast carcinoma, Lactobacillus casei, immune regulation, anti-tumor

中图分类号:

R392.1

梁争艳, 刘颖, 薛美兰, 刘佳, 梁惠. 干酪乳杆菌对二甲基苯蒽诱发大鼠乳腺肿瘤的抑制作用及其免疫学机制[J]. 癌变·畸变·突变, 2017, 29(1): 7-12.

LIANG Zhengyan, LIU Ying, XUE Meilan, LIU Jia, LIANG Hui. Inhibitory effect and immunological mechanism of Lactobacillus casei on induction of breast cancer by 7, 12-dimethylbenz (a)anthracene in rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(1): 7-12.

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干酪乳杆菌对二甲基苯蒽诱发大鼠乳腺肿瘤的抑制作用及其免疫学机制

Inhibitory effect and immunological mechanism of Lactobacillus casei on induction of breast cancer by 7, 12-dimethylbenz (a)anthracene in rats

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