4T1乳腺癌细胞株接种联合慢性束缚应激诱导乳腺癌合并抑郁小鼠模型构建探索
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1.河南中医药大学;2.河南省洛阳正骨医院(河南省骨科医院)

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Exploration of mouse model construction of breast cancer complicated with depression induced by using method of 4T1 breast cancer cell line inoculation combined with chronic restraint stress
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1.Henan University of Chinese Medicine;2.Henan Univesity of Chinese meidicine;3.Intensive Care Unit, Luoyang Orthopedic Hospital of Henan Province (Orthopedic Hospital of Henan Province)

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    摘要:

    【摘要】目的 研究4T1乳腺癌细胞株接种联合慢性束缚应激方法构建乳腺癌合并抑郁证小鼠模型核心行为症状、生物学指标、病理学等改变。方法 BABL/c小鼠随机分为正常组(Control)、束缚组(Stress)、移植瘤组(Tumor)和束缚 移植瘤组(Stress Tumor,S T),将4T1细胞株接种于Tumor和S T组小鼠腋下,待成瘤后,给予Stress和S T组小鼠束缚应激21天。造模期间监测各组小鼠体重、摄食量。实验结束后,采用糖水偏好试验、旷场试验、高架十字迷宫试验和强迫游泳试验评价各组小鼠抑郁样行为。小鼠断头处死后,测量小鼠瘤体重量和体积;采用Elisa方法检测各组小鼠血清肿瘤标志物:糖类抗原(CA199)、癌胚抗原(CEA)、血管内皮生长因子(VEGF)以及相关神经递质:5-羟色胺(5-HT)、去甲肾上腺素(NE)、皮质酮(CORT)的含量;运用HE染色法观察小鼠肿瘤和海马组织病理学改变。结果 S T组小鼠体重、摄食量显著降低,瘤体重量和体积明显增大,血清肿瘤标志物(CA199、CEA、VEGF)水平显著升高,快感和对新环境的探索欲望减弱,紧张和绝望行为显著增强,血清神经递质5-HT和NE水平显著降低,CORT水平显著升高;另外肿瘤组织细胞排松散,间质减少,病理性核分类相增多,海马CA3区神经元细胞排列和形态紊乱,核内空泡化样改变明显。结论 4T1乳腺癌细胞株接种联合慢性束缚应激诱导的乳腺癌合并抑郁小鼠模型出现了乳腺癌和抑郁症双重典型症状和生物学指标改变,可为乳腺癌合并抑郁实验研究提供较好的模型参考。

    Abstract:

    【Abstract】Objective To study the core behavioral symptoms, biological indicators and pathological changes of the mouse model construction of breast cancer complicated with depression induced by using method of 4T1 breast cancer cell line inoculation combined with chronic restraint stress (CRS). Methods BABL/c mice were randomly divided into control group, stress group, tumor group and stress combined with tumor group (S T). 4T1 cell lines were inoculated into the underarm of mice in tumor and S T groups. After tumor formation, mice in the stress and S T groups were subjected to CRS for 21 days. Body weight and food intake of each group were monitored during modeling. After the experiment, depression-like behavior of mice in each group was evaluated by sucrose preference test, open field test, elevated plus-maze test, and forced swimming test. After the mice were decapitated, the weight and volume of mouse tumor were measured. Serum tumor markers including carbohydrate antigen (CA199), carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF) and related neurotransmitters including 5-hydroxytryptamine (5-HT), norepinephrine (NE) and corticosterone (CORT) were determined by using Elisa method. HE staining was used to observe the histopathological changes of hippocampus and tumor of mice. Results In mice of S T group, the body weight and food intake were significantly decreased, tumor weight and volume were significantly increased, serum tumor markers (CA199, CEA, VEGF) levels were significantly increased, pleasure and desire to explore the new environment were weakened, stress and despair behaviors were significantly increased, serum neurotransmitters 5-HT and NE levels were significantly decreased, and CORT levels were significantly increased. In addition, the cell arrangement of tumor tissue was loose, the interstitial was reduced, the pathological nuclear classification phase was increased, the arrangement and morphology of neurons in the CA3 region of hippocampus were disordered, and the nuclear vacuolation-like changes were obvious. Conclusion The mouse model of breast cancer complicated with depression induced by 4T1 breast cancer cell line inoculation combined with chronic restraint stress showed the dual typical symptoms and biological indicators of breast cancer and depression, which can provide a good model reference for the experimental study of breast cancer complicated with depression.

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  • 收稿日期:2023-05-04
  • 最后修改日期:2023-07-19
  • 录用日期:2024-02-26
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