促渗剂氮酮对斑马鱼胚胎的透皮作用及毒性影响.pdfVIP

Toxicity and permeation of laurocapram in zebrafish (Danio rerio) embryos Xiqiang Chen, liwen Han, Ximin Wang, Sifeng Wang, Hairong Hou,Kechun Liu. Department of drugscreen, Shandong Key Laboratory of Biosensors, Biology Institute of Shandong Academy of Sciences，Jinan 250014,China. ABSTRACT laurocapram (1-dodecylazacycloheptan-2-one) is a widely used skin penetration agent. Embryos were treated with 0.01 μm/mL to 0.12 μm/mL laurocapram for 24 h post-fertilization during budding of intersegmental vessels (ISVs) to study laurocapram toxicity in zebrafish embryos. The results showed that the appearance of a large number of hook-type tails, low heart rates, and high mortality could be avoided with laurocapram administration at concentrations below 0.02 μm/mL. In the presence of laurocapram, 0.08 μm/mL resveratrol and 0.1 μm/mL indirubin could significantly inhibit the growth of ISVs in zebrafish after 24 h incubation (p 0.01). High-performance liquid chromatography analysis showed that increased amounts of indirubin were absorbed by embryos with the addition of laurocapram, indicating that appropriate doses of laurocapram could effectively promote absorption of compounds in zebrafish. Keywords: laurocapram; zebrafish; toxicity; permeation 促渗剂氮酮对斑马鱼胚胎的透皮作用及其毒性影响 陈锡强，韩利文，王希敏，王思锋，侯海荣，刘可春， 山东省科学院生物研究所 山东省济南市 250014 摘要 目的氮酮（1-十二烷基氮杂环庚烷-2-酮）是一种广泛应用促透皮剂，本 实验考察氮酮对斑马鱼胚胎的安全浓度范围与其促进透皮作用。方法 采用多个 浓度氮酮溶液处理24hpf 斑马鱼胚胎，作用24 小时后观察氮酮对斑马鱼胚胎的 发育的毒性反应；分别考察氮酮促进白藜芦醇透皮后，对斑马鱼胚胎节间血管生 成的影响；考察氮酮与靛玉红同时作用对斑马鱼胚胎节间血管生成的影响，应用 高效液相检测斑马鱼体内靛玉红的含量。 结果 在氮酮浓度低于0.02 μm/mL ，斑马鱼胚胎的死亡率、翘尾畸形与心率慢的 毒性反应都会显著降低。在0.02 μm/mL 氮酮存在的条件下，白藜芦醇抑制节间 血管生成的作用显著增强（p0.01 ）；靛玉红抑制节间血管生成的作用也增加 （p0.01 ）；斑马鱼胚胎体内靛玉红的含量明显增加。结论 0.02 μm/mL 氮酮对 斑马鱼胚胎具有良好的安全性，具有促进天然产物透皮的作用。 Background The zebrafish (Danio rerio) is well-known animal model used for screening new therapeutic agents f