基于斑马鱼模型的26种常见骨伤科中药材的毒性筛选

陈颖; 汪晶; 陈书芹; 景莉君; 韦英杰

基于斑马鱼模型的26种常见骨伤科中药材的毒性筛选

陈颖^1,2,
汪晶²,
陈书芹¹,
景莉君¹,
韦英杰^1,2,

1.
南京中医药大学药学院，江苏南京 210023
2.
江苏省中医药研究院，国家中医药管理局中药口服释药系统重点研究室，江苏南京 210028

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出版历程
- 收稿日期: 2016-05-05
- 修回日期: 2016-07-09
- 刊出日期: 2016-09-10

Screening on Toxicity of 26 Kinds of Common Orthopedic Herbal Medicine Using Zebrafish Model

1.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
2.
Key Laboratory of Oral Drug Delivery System of Chinese Meteria Medica of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, China

摘要

摘要: 目的利用斑马鱼毒性模型评价26种常见伤科中药材的安全性。方法将受精后1 d（1 dpf）的健康斑马鱼胚胎置于不同浓度药味水煎液中，观察记录给药后1~5 d的死亡情况，显微检视3 dpf或以后斑马鱼幼鱼的形态，同时设置0.4%DMSO溶媒对照组。用SPSS16.0计算不同药味水煎液在6 dpf的鱼半数致死浓度LC₅₀。结果 13种药味（续断、知母、乳香加没药、补骨脂、独活、牛膝、制何首乌、蛇床子、木香、土鳖虫、淫羊藿和五加皮）水煎液致斑马幼鱼脏器形态明显改变，毒性主要表现为卵黄囊肿大、变形、变黑，心包水肿、出血等，且它们的鱼LC₅₀值较低（16.9~689.7 μg/mL）。其余13种药味（鹿衔草、千年健、苏木、巴戟天、龟甲、骨碎补、丹参、狗脊、桑寄生、鸡血藤、熟地黄、女贞子、杜仲），未见鱼脏器毒性，且致鱼死亡浓度高（在2 000 μg/mL以上），较安全。结论用斑马鱼模型成功的筛选了26种常见骨伤科中药的毒性，为骨伤科中药临床合理应用提供参考。斑马鱼模型具有简单、高效、实时动态的优势，使中药在体毒性规模化筛选成为可能。
- 斑马鱼 /
- 骨伤科中药 /
- 毒性 /
- 筛选
Abstract: OBJECTIVE Toxicity model of zebrafish was used to evaluate safety of 26 kinds of common orthopedic herbal medicine. METHODS Zebrafish embryo at 1 day post fertilization (dpf) were exposed with various concentration of water decoction; the death number of the embryos or larvals was counted from 1dpf to 6 dpf; embryonic micro-morphology of zebrafish (3dpf) was observed and pictures were taken that compared with 0.4% DMSO; LC₅₀ value at 6dpf was calculated by SPSS16.0. RESULTS The results indicated that 13 kinds of water decoction of herbal medicines (Dipsaci Radix， Anemarrhena Rhizoma， Olibanum and Myrrha， Psoraleae Fructus， Angelicae Pubescentis Radix， Achyranthis Bidentatae Radix， Polygoni multiflori Radix， Cnidii Fructus， Aucklandiae Radix， Eupolyphaga Steleophaga， Epimedii Folium and Acanthopanacis Cortex) can cause obvious organ toxicity to juvenile zebrafish， such as yolk sac swelling， deformation， black， pericardial edema and bleeding， and their LC₅₀ values were low (16.9~689.7 μg/mL)， while the other 13 herbal medicines are relatively safe (Pyrolae Herba， Homalomena Rhizoma， Sappan Lignum， Morindae Officinalis Radix， Testudinis Carapax Et Plastrum， Drynariae Rhizoma， Salviae miltiorrhizae Radix Et Rhizoma， Cibotii Rhizoma， Taxilli Herba， spatholobi CauLis， Rehmanniae Radix Praeparata， Ligustri Lucidi Fructus and Eucommiae Cortex)， no fish organ toxicity was observed， and their concentration caused zebrafish death was usually at high levels (above 2 000 μg/mL). CONCLUSION Zebrafish model was successfully used for screening toxicity of 26 common orthopedic herbal medicine， which may provide useful information for reasonable application of them. Zebrafish model has advantages of simplicity， high efficiency and real-time observation， which made large scale toxicity screening of herbal medicine in vivo style possible.
- zebrafish /
- orthopedic herbal medicine /
- toxicity /
- screening

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