类香豆素成分B系列化合物(编号1-14)抗肿瘤活性研究毕业论文
2022-07-14 23:01:32
论文总字数:21379字
摘 要
血管新生是从已有血管发芽生成新血管的过程,有研究表明,血管新生与肿瘤的发生密切相关,即具有血管新生抑制活性的药物可能成为抗肿瘤的候选药物。对于血管新生这一体内动态生理过程,传统的药理模型和评价指标均不能很好地开展深入,系统的研究。斑马鱼具有体积小、繁殖速度快和胚胎透明等特点,并且与人类共享约87%的同源基因,已成为一种重要的模式生物受到广泛关注。利用斑马鱼建立血管新生研究模型具有快速、简便、并能实时反映药物的体内作用效果等优点,已成为相关领域研究人员的有力工具。
岩白菜素作为镇咳祛痰药,已被《中华人民共和国药典》收载。近年来,有学者对岩白菜素母核进行结构改造得到的部分岩白菜素衍生物具有体外抑制肿瘤细胞增殖活性,因此,在前期结构修饰的基础上,对岩白菜素B-O及其衍生物B-1、B-2、B-3对几种肿瘤细胞系开展体外抗肿瘤活性进行初步筛选,并通过斑马鱼模型评价其体内血管新生活性。结果表明:虎耳草素衍生物相对于母体化合物,对几种肿瘤细胞系的抑制活性均有所提高,但通过斑马鱼血管新生研究模型发现,虎耳草素衍生物抑制血管新生活性不明显,表明虎耳草素衍生物的抑制肿瘤增殖的机制仍有待进一步研究。
关键词:岩白菜素衍生物 斑马鱼模型 血管新生
Research in antitumor and antiangiogenics of bergenin derivatives
Abstract
Angiogenesis is the process of generating from existing blood vessels sprouting of new blood vessels, studies have shown that angiogenesis is closely related to tumorigenesis, ie with angiogenesis inhibitory activity of anti-tumor drugs may become drug candidates. For the in vivo angiogenesis dynamic physiological processes, the traditional model and pharmacological evaluation are not well studied in-depth, systematic conduct. Zebrafish has a small, fast reproduction and embryo transparency and other characteristics, and humans share about 87% homologous genes, has become an important model organism attracted widespread attention. Angiogenesis in zebrafish research model to establish a rapid, simple, and can reflect the real-time in vivo effects of drugs, etc., has become a powerful tool for researchers in related fields.
Bergenin as antitussive and expectorant drugs, has been "People's Republic of China Pharmacopoeia" set. In recent years, some scholars bergenin nucleus of partial derivatives of structural transformation bergenin obtained with in vitro inhibition of tumor cell proliferation, therefore, on the basis of preliminary structural modification of its derivatives bergenin B-O B -1, B-2, B-3 against several tumor cell lines in vitro anti-tumor activity carried out initial screening and evaluation of its angiogenic activity in vivo zebrafish model through the results showed that: saxifrage prime derivatives with respect to the parent compounds for inhibitory activity in several tumor cell lines were improved, but by zebrafish model of angiogenesis research found saxifrage prime derivatives inhibit the angiogenic activity is not obvious, indicating inhibition of tumor hormone derivatives saxifrage proliferation mechanism remains to be further studied.
Key words: bergenin derivatives ; zbrafish model ; angiogenesis
目录
摘要 I
Abstract II
第一章 综述 1
1.1岩白菜素研究概况 1
1.1.1 植物来源与分布 2
1.1.2岩白菜素的结构及衍生物 2
1.1.3 药理学研究 4
1.1.5毒理学研究 5
1.2抗肿瘤活性与血管新生的关系 6
1.2.1血管生成与肿瘤的生长和转移密切相关 6
1.2.2肿瘤血管生成的过程 6
1.3斑马鱼在抗血管新生研究的应用和独特优势 7
1.3.1传统药物蹄选模型不足之处 7
1.3.2斑马鱼在药物蹄选中的优势 7
1.3.3斑马鱼在抗血管生成药物筛选中的应用 7
1.4斑马鱼在毒理学研究中的应用 8
第二章 体外抗肿瘤初步筛选研究 9
2.1实验材料 9
2.1.1细胞株 9
2.1.3 主要试剂与耗材 9
2.1.4 主要仪器 9
2.2实验方法 10
2.2.1 细胞培养 10
2.2.2 CCK-8细胞增殖活力检测试验 12
2.3 实验结果 13
第三章 岩白菜素衍生物对斑马鱼血管抑制活性实验 16
3.1实验材料 16
3.1.1 实验动物 16
3.1.2 药物与试剂 16
3.1.3 主要实验仪器 16
3.2 主要实验溶液和药物的配制 16
3.3 斑马鱼胚胎的培养 17
3.4 实验方法 17
3.4.1转基因斑马鱼血管新生抑制模型的建立 17
3.4.2药物处理 17
3.4.3表型观察及数据处理 18
3.5 实验结果 18
参考文献……………………………………………………………………………………………………………………………….......21
致谢………………………………………………………………………………………………………………………………………..........23
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