基于斑马鱼的对香豆酸甲酯的抗血管新生活性研究(任务书,开题报告,外文翻译,论文9000字)
摘 要
血管生成是许多生理和病理过程中的关键一环。血管抑制活性化合物可作为治疗异常血管生成疾病的治疗药物。对香豆酸甲酯（pCAME）是闭鞘姜（Koen）Sm的成分（姜科）。 闭鞘姜是生长在菲律宾，印度，斯里兰卡和马来西亚的一种草本植物。种植物的根茎可以用于治疗蠕虫，消化不良，卡他性发热和一些皮肤病。已有研究，pCAME具有抗黑变性，抗氧化性和抗微生物活性，引起了我们对其血管活性的研究的兴趣。
斑马鱼因为其基因与哺乳类动物具有高度保守性这一特点使之成为研究化学物质临床安全性的理想生物模型。本实验选择了转基因斑马鱼（fli-1：EGFP）模型，发现pCAME抑制了斑马鱼发育中体节间与肠下网血管的生成。为进一步研究，我们选用了vegfa，ang-1，ang-2及其受体flt-1，flk-1，tie-1，tie-2血管发育相关基因作为代表来研究pCAME诱导抗血管生成的分子机制。发现pCAME抑制了vegf / vegfr和ang / tie信号通路的表达。PCAME有成为血管生成抑制剂的潜能，可作为先导化合物开发成抗血管生成药物。
关键词： 体节间血管 肠下静脉血管 对香豆酸甲酯 斑马鱼 抗血管新生
ABSTRACT
Angiogenesis is a key link in many physiological and pathological processes. Angiostatic compounds can be used as therapeutic agents for treating abnormal angiogenic diseases.Methyl coumarate (pCAME) is a component of Koen Sm (Gingeraceae). Ginger is a herb that grows in the Philippines, India, Sri Lanka and Malaysia. The rhizomes of the plants can be used to treat worms, indigestion, catarrhal fever and some skin diseases. It has been studied that pCAME has anti-blackening, anti-oxidation and anti-microbial activity, which has aroused our interest in the study of its vasoactive activity.
Zebrafish is an ideal biological model for studying the clinical safety of chemical substances due to its highly conserved nature of mammals and mammals. In this experiment, the transgenic zebrafish (fli-1:EGFP) model was selected and it was found that pCAME inhibited the formation of intravascular and subinvasive vasculature in zebrafish development. For further study, we used vegfa, ang-1, ang-2 and its receptors flt-1, flk-1, tie-1, tie-2 angiogenesis-related genes as representatives to study pCAME-induced anti-angiogenic molecules. mechanism. It was found that pCAME inhibits the expression of vegf / vegfr and ang / tie signaling pathways. PCAME has the potential to become an angiogenesis inhibitor and can be developed as an anti-angiogenic agent as a lead compound.
Keywords:ISV SIV pCAME Danio rerio Antiangiogenesis
目 录
摘 要 Ⅰ
ABSTRACT Ⅱ
第一章 文献综述 1
1.1斑马鱼模型的介绍与应用 1
1.1.1 斑马鱼简介 1
1.1.2斑马鱼模型在发现天然产物生物活性分子的意义 2
1.1.3斑马鱼在筛选抗血管抑制剂方面的的应用 3
1.2 新生血管抑制剂的研究 4
1.2.1 新生血管抑制剂的研究进展 4
1.2.2 筛选血管抑制剂的模型 4
1.3 对香豆酸甲酯的简介 6
第二章 实验材料与方法 7
2.1 引言 7
2.2 实验材料 7
2.2.1药物简介 7
2.2.2 主要试剂和仪器 8
2.2.3 对香豆酸甲酯体内抗血管新生活性检测方法 9
第三章 实验结果与讨论 14
3.1 对香豆酸甲酯对转基因斑马鱼体节间血管（ISV）和肠下静脉血管（SIV）的抑制作用 14
3.2定量评价对香豆酸甲酯对斑马鱼体节间血管（ISV）和肠下静脉血管（SIV）生成模型的抑制效果 15
3.3 qRT-PCR实验结果 17
3.4 实验总结 18
参考文献 19
致谢 22
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