Zhou Juan, Xu Yi-Qiao, Guo Sheng-Ya, Li Chun-Qi
Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, PR China; Hunter Biotechnology, Inc., Transfarland, Hangzhou, Zhejiang Province 311231, PR China.
Hunter Biotechnology, Inc., Transfarland, Hangzhou, Zhejiang Province 311231, PR China.
J Pharmacol Toxicol Methods. 2015 Mar-Apr;72:47-52. doi: 10.1016/j.vascn.2014.12.002. Epub 2014 Dec 12.
Hyperlipidemia is the most common form of dyslipidemia, which is the key risk factor for cardiovascular disease and stroke. The development of effective and safe drug treatments for hyperlipidemia has been proven challenging.
In this study, taking advantage of the transparency of larval zebrafish, we developed a zebrafish hyperlipidemia model for drug screening and efficacy assessment. Zebrafish at 5 d.p.f (days post fertilization) were fed with 0.1% egg yolk for 48 h (hours), followed by drug treatment for 24h or 48 h. Tested drugs were administered into the zebrafish by direct soaking. Drug effect was evaluated based on quantitative analysis of Oil Red O (ORO) in zebrafish vena caudalis.
All 5 human hypolipidemic drugs (simvastatin, lovastatin, ezetimibe, bezafibrate and hyodesoxycholic acid) showed significant hypolipidemic effects (p<0.01) in a dose-dependent manner in the zebrafish hyperlipidemia model. 'We also found a well-known Chinese tea Pu-erh tea significantly reduced lipids in this model (p<0.001 and p<0.01).
Our results demonstrate that the zebrafish hyperlipidemia model developed and validated in this study could be used for in vivo hyperlipidemia studies and drug screening and for assessing hypolipidemic drugs with different mechanisms.
高脂血症是血脂异常最常见的形式，是心血管疾病和中风的关键危险因素。事实证明，开发有效且安全的高脂血症药物治疗具有挑战性。
在本研究中，利用斑马鱼幼体的透明性，我们开发了一种用于药物筛选和疗效评估的斑马鱼高脂血症模型。将受精后5天（d.p.f）的斑马鱼用0.1%的蛋黄喂养48小时（h），然后进行24小时或48小时的药物治疗。通过直接浸泡将受试药物施用于斑马鱼。基于对斑马鱼尾静脉中油红O（ORO）的定量分析来评估药物效果。
在斑马鱼高脂血症模型中，所有5种人类降血脂药物（辛伐他汀、洛伐他汀、依折麦布、苯扎贝特和猪去氧胆酸）均呈剂量依赖性地显示出显著的降血脂作用（p<0.01）。我们还发现一种著名的中国茶——普洱茶在该模型中能显著降低血脂（p<0.001和p<0.01）。
我们的结果表明，本研究中开发并验证的斑马鱼高脂血症模型可用于体内高脂血症研究和药物筛选，以及评估具有不同作用机制的降血脂药物。
