秀丽隐杆线虫作为药物筛选及研究模型广泛应用于各研究领域,例如发育生物学、化学生物学、脂肪代谢和肥胖症、衰老、神经退行性疾病、环境毒理学以及癌症研究等。由于线虫的体型很小(成虫只有约1毫米),给药方式不同导致药物吸收效率不同,所以不同研究结果之间存在差别并且难以进行比较分析。
中国科学院昆明植物研究所罗怀容研究组以低水溶性的白藜芦醇和易溶于水的氟尿苷(FUDR)作为参考药物,五种常用的给药方式分别处理线虫,评价了线虫对于脂溶性和水溶性药物的吸收效率,揭示了线虫不同给药方式下药物吸收代谢的规律。研究结果表明白藜芦醇和FUDR的浓度在用五种给药方法培养的线虫体内逐渐的升高,在12-24小时达到最高,并随着培养时间的推移慢慢降低。同时,给药的浓度越高,线虫代谢和外排越快。线虫对低水溶性的白藜芦醇和易溶于水的FUDR具有相似的吸收和代谢模式。由于用于培养线虫的培养基内的药物被活的细菌吸收,导致培养基中药物浓度降低较快,线虫食用细菌为灭活状态时要比食用细菌为存活状态时的吸收效率高。在五种培养方法中,NGM dead method 和liquid growing method培养的线虫吸收药物的效率最高。线虫体内的药物浓度可以换算为小鼠体内的药物剂量,为线虫给药剂量和哺乳动物给药剂量之间的转换提供了一个桥梁。
上述研究结果以Drug Absorption Efficiency in Caenorhbditis elegans Delivered by Different Methods为题发表在《公共科学图书馆—综合》(PLoS ONE)上。
该研究工作得到中国科学院百人计划项目、云南省高端科技人才项目、植物化学与西部植物资源持续利用国家重点实验室项目的资助。(生物谷Bioon.com)
DOI:10.1371/journal.pone.0056877
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Drug Absorption Efficiency in Caenorhbditis elegans Delivered by Different Methods
Shan-Qing Zheng, Ai-Jun Ding, Guo-Ping Li, Gui-Sheng Wu, Huai-Rong Luo
Caenorhbditis elegans has being vigorously used as a model organism in many research fields and often accompanied by administrating with various drugs. The methods of delivering drugs to worms are varied from one study to another, which make difficult in comparing results between studies. Methodology/Principal Findings We evaluated the drug absorption efficiency in C. elegans using five frequently used methods with resveratrol with low aqueous solubility and water-soluble 5-Fluoro-2′-deoxyuridine (FUDR) as positive compounds. The drugs were either applied to the LB medium with bacteria OP50, before spreading onto Nematode Growth Medium (NGM) plates (LB medium method), or to the NGM with live (NGM live method) or dead bacteria (NGM dead method), or spotting the drug solution to the surface of plates directly (spot dead method), or growing the worms in liquid medium (liquid growing method). The concentration of resveratrol and FUDR increased gradually within C. elegans and reached the highest during 12 hours to one day and then decreased slowly. At the same time point, the higher the drug concentration, the higher the metabolism rate. The drug concentrations in worms fed with dead bacteria were higher than with live bacteria at the same time point. Consistently, the drug concentration in medium with live bacteria decreased much faster than in medium with dead bacteria, reach to about half of the original concentration within 12 hours. Conclusion Resveratrol with low aqueous solubility and water-soluble FUDR have the same absorption and metabolism pattern. The drug metabolism rate in worms was both dosage and time dependent. NGM dead method and liquid growing method achieved the best absorption efficiency in worms. The drug concentration within worms was comparable with that in mice, providing a bridge for dose translation from worms to mammals.