异甘草素对斑马鱼胚胎发育、血管生成和心脏的影响
Effects of Isoliquiritigenin on Embryonic Development,

中文摘要： 目的 研究异甘草素对斑马鱼 Danio rerio var.胚胎发育、血管生成以及心脏的影响。 方法 异甘草素处理受精后10 h、24 h的正常斑马鱼胚胎；显微镜下观察并记录药物作用12 h、24 h、36 h、48 h后斑马鱼胚胎发育、血管生成、心率以及心脏形态。 结果 异甘草素浓度为4 μg·mL -1时可轻度抑制斑马鱼胚胎尾部发育，浓度为12 μg·mL -1及以上时会严重抑制胚胎发育。异甘草素具有抑制斑马鱼胚胎血管生成作用，浓度为2 μg·mL -1时即可抑制血管的生成，8 μg·mL -1时甚至完全抑制尾部静脉血管的生成。异甘草素可显著降低斑马鱼胚胎心率，中低剂量下，心率随着作用时间增加呈先降后升的趋势，对心脏形态无影响；高剂量下，心率随作用时间增加而降低，异甘草素致斑马鱼胚胎心包与卵黄囊肿大。 结论 中低剂量异甘草素具有良好的抗血管生成和减慢心率的作用，高剂量时随着作用时间延长具有一定的抑制发育作用。
英文摘要： Objective To study the effects of isoliquiritigenin on zebrafish ( Danio rerio var.) embryonic development, angiogenesis and heart function. Methods The zebrafish embryos after 10 h and 24 h post fertilization were treated with isoliquiritigenin for 12 h; 24 h; 36 h and 48 h; and the effects of isoliquiritigenin on the fertilization development; angiogenesis and cardiac morphology were investigated and recorded by microscopy. Results The results showed that isoliquiritigenin treatment slightly inhibited the development of zebrafish embryo tail in a concentration of 4 μg·mL -1, and the development of zebrafish embryo tail could be severely inhibited by 12 μg·mL -1 of isoliquiritigenin; Isoliquiritigenin treatment significantly inhibited the angiogenesis of zebrafish embryos in a concentration of 2 μg·mL -1, and the development of zebrafish embryo tail could be completely inhibited the angiogenesis by 8 μg·mL -1 of isoliquiritigenin; At the low or medium doses of isoliquiritigenin treatment, the heart rate of zebrafish embryos was firstly reduced and then increased, but with no obviously change in cardiac morphology. At the high doses, isoliquiritigenin disturbed the heart development of zebrafish, and caused the zebrafish's pericardium and saccus omphaloentericus swelling. Conclusion Isoliquiritigenin has a good effect on anti-angiogenesis and slowing down the heart rate at the low or medium doses, but inhabits the development of zebrafish embryos at the high doses. 2018,37(6): 672-677 收稿日期：2018-04-04 分类号：R965.1;Q954.48 基金项目：国家自然科学基金项目（81503346，81403149）；成都中医药大学科技创新基金项目（ZRQN1770，ZRQN1764）；四川省中医药管理局科技创新项目（2016Q054） 作者简介：何俊霖(1995—),女,硕士研究生,从事中药药理与毒理研究,E-mail:1206810161@qq.com *通信作者：李玉芝,博士,副教授,从事中药药理研究,E-mail:liyuzhi5654@163.com;彭成,博士,研究员,博士生导师,主要从事中药药理与毒理研究,E-mail:pengchengchengdu@126.com 参考文献： 彭蕴茹, 韦英杰, 丁永芳, 等. 2017. 基于斑马鱼模型的药物毒性研究进展与中药毒性研究新策略[J]. 中草药, 48(1): 17-30. 展翔. 2018. 异甘草素对失血性休克大鼠动物模型肾脏EPCR表达的影响及其肾脏功能保护机制[J]. 实用药物与临床, 21(1): 1-4. Carmeliet P, Jain RK. 2000. Angiogenesis in cancer and other diseases[J]. Nature, 407(6801): 249-257. Gao F, Zhang J, Fu C, et al. 2017. iRGD-modified lipid-polymer hybrid nanoparticles loaded