小鼠经骨髓注射肺转移和术后复发模型的建立
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1.上海中医药大学基础医学院,上海 201203; 2.上海交通大学医学院附属新华医院,上海 200092; 3. 上海中医药大学科技实验中心,上海 201203

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Establishment of a model of lung metastasis and recurrence of mice after bone marrow injection
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1.School of Basic Medical Science,Shanghai University of TCM,Shanghai 201203,China. 2. Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092. 3. Science and Technology Experimental Center, Shanghai University of TCM, Shanghai 201203

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    摘要:

    目的 建立经骨髓注射肺转移和术后复发模型,揭示骨髓注射法构建模型的优越性和可行性,为研 究恶性肿瘤肺转移提供新的研究基础。 方法 将小鼠分为乳垫注射组、皮下注射组、尾静脉注射组和骨髓注射组。使用 4T1 细胞构建不同的模型,观察不同组别原发肿瘤的生长、生存期和转移效率。注射不同数量的 4T1 细胞,观察肺部转移发生的时间。经骨髓注射 4T1-luc 细胞构建术后复发模型,将小鼠分为假截肢组、第 3 天截肢组、第7天截肢组和第 10 天截肢组,通过活体成像观察小鼠肺转移情况。 结果 与乳垫注射法和皮下注射法相比,骨髓注射法对原发肿瘤的生长没有影响,但其生存期显著缩短。与乳垫注射法、皮下注射法和尾静脉注射法相比,骨髓注射法肺转移效率最高。骨髓注射法仅需 1×105 个 4T1 细胞数量即可在第 12 天发生肺转移。经骨髓注射的模型小鼠在截肢后,仍会造成肺转移和原发肿瘤的复发。 结论 成功建立经骨髓注射肺转移小鼠模型和术后复发小鼠 模型,使用该注射方法的小鼠模型具有生存期短和高转移效率的特点,可用于恶性肿瘤肺转移的机制研究及药物筛选。

    Abstract:

    Objective To establish a model of lung metastasis by bone marrow injection and a model of tumor recurrence after surgery to reveal the superiority and feasibility of the model of bone marrow injection to provide a new research basis for studying lung metastasis of malignant tumors. Methods The mice were divided into a mammary fat pad injection group, a subcutaneous injection group, a tail vein injection group, and a bone marrow injection group. Different models of 5 × 105 4T1 cells were injected via mammary fat pad injection, subcutaneous injection, tail vein injection, and bone marrow injection, and the growth, survival period, and lung metastasis efficiency of the primary tumors of model mice under different modeling method were observed. Different numbers of 4T1 cells were injected and the time of lung metastasis was observed. 4T1-luc cells were injected into the bone marrow to construct a postoperative tumor recurrence model. The mice were divided into a sham amputation group, a 3rd day amputation group, a 7th day amputation group, and a 10th day amputation group. Live imaging was performed every 7 days to observe lung metastasis in mice, while imaging was performed in the lungs of mice in the pseudo-amputation group and the 7th day amputation group to confirm the success of model construction. Results Compared with mammary fat pad injection and subcutaneous injection, bone marrow injection had no effect on the growth of the primary tumor, but the associated survival time was significantly shortened. Compared with mammary fat pad injection, subcutaneous injection, and tail vein injection, bone marrow injection had the highest lung metastasis efficiency. The bone marrow injection method required only 1 × 105 4T1 cells to cause lung metastasis on the 12th day. Mice with bone marrow injection still exhibited lung metastasis and recurrence of primary tumor after amputation. Conclusions A mouse model of lung metastasis can be successfully established by bone marrow injection along with a mouse model of tumor recurrence after surgery. The mouse model created using this injection method has the characteristics of a short survival time and high metastasis efficiency. It can be used to study the mechanism of lung metastasis of malignant tumors and the related screening of drugs for treating malignant tumors.

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焦肖宁,侯怡飞,朱杨壮壮,苏琳,张飞,陈晓,朱诗国,韦璐瑶,王万涛,王杰,朱娴丹,邹纯朴,胥孜杭.小鼠经骨髓注射肺转移和术后复发模型的建立[J].中国实验动物学报,2020,28(5):610~617.

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  • 收稿日期:2020-06-15
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  • 在线发布日期: 2020-11-25
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