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中国医药生物技术 2007, Vol. 2 Issue (1) :13-13-17    DOI:
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人海绵状血管瘤动物模型的建立和治疗药物的筛选
张文健[1]; 吴练秋[1]; 顾锋[2]; 叶丽亚[1]; 辛育龄[3]; 杨治华[4]; 娄晋宁[1]
[1]中日友好医院 临床医学研究所;
[2]中国医学科学院 北京协和医院 内分泌科
[3]中日友好医院 中日友好医院 血管外科;
[4] 中国医学科学院 肿瘤研究所
Establishment of an animal model of human cavernous angioma for drug screening
ZHANG Wen-jian[1];WU Lian-qiu[1];GU Feng[2];YE Li-ya[1];XIN Yu-ling[3];YANG Zhi-hua[4];LOU Jin-nin[1]
1.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029,China;
2. Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences;
3.Department of Vascular Surgery, China-Japan Friendship Hospital Cancer Institute;
4. Chinese Academy of Medical Sciences Institute of Clinical Medical Sciences

摘要
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摘要 


目的
建立人海绵状血管瘤的动物模型,并用于药物筛选。

方法
用荆豆凝集素包被的免疫磁珠分离和纯化人海绵状血管瘤内皮细胞(HCAEC)。将HCAEC(2.5×106个)与人肝癌细胞Bel-7402(5×105个)混合接种于裸鼠皮下,建立海绵状血管瘤的动物模型。通过绿色荧光蛋白示踪和组织学检查分析血管瘤中内皮细胞的来源和血管瘤的病理特征。另外,应用血管瘤内皮细胞和血管瘤动物模型筛选血管瘤的治疗药物。

结果
HCAEC与Bel-7402细胞共移植于裸鼠皮下后7~9 d即可见接种局部形成血管瘤样结构。组织学检查显示血管瘤模型的组织学特征与人的海绵状血管瘤非常相似。细胞绿色荧光蛋白示踪显示绿色荧光蛋白存在于血管瘤的管壁,表明这些细胞来源于接种的HCAEC。药物筛选发现876-3,一种从中药中提取的单体,体外明显抑制HCAEC增殖,体内对血管瘤具有良好治疗作用。

结论
HCAEC与肝癌细胞共移植在裸鼠皮下可以形成人源化血管瘤动物模型,这种血管瘤动物模型可以用于治疗药物的筛选。

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张文健
吴练秋
顾锋
叶丽亚
辛育龄
杨治华
娄晋宁
关键词血管瘤,海绵状   内皮细胞   动物模型   药物评价,临床前     
Abstract
Objeetive
To establish an animal model of human cavernous angioma for drug screening.

Methods
Endothelial cells derived from human cavernous angioma (HCAEC) were isolated and purified by Ulex europaeus agglutinin-1(UEA-1)-conjugated magnetic beads. An animal model of human cavernous angioma was established by co-inoculating HCAEC and human liver cancer cells (Bel-7402) into immune-deficient nude mice subcutaneously. GFP-tagging and histopathological examinations were used to analyze the source of endothelial cells and pathological features in the angioma tissue. In addition, drugs for angioma were screened by HCAEC assay in vitro, and using the angioma model in vivo.

Results
An angioma-like structure was found on the site of co-inoculation of HCAEC (2.5×106) and Bel-7402 cells (5×105) 7-9 days after the transplantation. The histological feature of the angioma-like tissues was similar to that of a human angioma. GFP-tagging showed green fluorescence on the vascular wall of the angioma-like tissues, suggesting that the endothelial cells came from the inoculated HCAEC. Drug screening found that 876-3, an extract from a Chinese traditional medicine, was an effective drug for inhibiting the proliferation of HCAEC in vitro, and for treating the angioma in vivo.

Conclusions
An animal model of human angioma can be established by co-inoculating HCAEC and Bel-7402 cells into immune-deficient nude mice, and this animal model can be used in drug screening for angioma.
KeywordsHemangioma, cavernous   Endothelial cells   Models, animal   Drug evaluation, priclinical     
Received 2007-01-18;
Corresponding Authors: 娄晋宁   
引用本文:   
张文健 吴练秋 顾锋 叶丽亚 辛育龄 杨治华 娄晋宁 .人海绵状血管瘤动物模型的建立和治疗药物的筛选[J]  中国医药生物技术, 2007,V2(1): 13-13-17
ZHANG Wen-jian[1];WU Lian-qiu[1];GU Feng[2];YE Li-ya[1];XIN Yu-ling[3];YANG Zhi-hua[4];LOU Jin-nin[1].Establishment of an animal model of human cavernous angioma for drug screening[J]  , 2007,V2(1): 13-13-17
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