秀麗隱桿線蟲作為藥物篩選及研究模型廣泛應(yīng)用于各研究領(lǐng)域,,例如發(fā)育生物學(xué)、化學(xué)生物學(xué),、脂肪代謝和肥胖癥,、衰老、神經(jīng)退行性疾病,、環(huán)境毒理學(xué)以及癌癥研究等,。由于線蟲的體型很?。ǔ上x只有約1毫米),給藥方式不同導(dǎo)致藥物吸收效率不同,,所以不同研究結(jié)果之間存在差別并且難以進(jìn)行比較分析,。
中國(guó)科學(xué)院昆明植物研究所羅懷容研究組以低水溶性的白藜蘆醇和易溶于水的氟尿苷(FUDR)作為參考藥物,五種常用的給藥方式分別處理線蟲,,評(píng)價(jià)了線蟲對(duì)于脂溶性和水溶性藥物的吸收效率,,揭示了線蟲不同給藥方式下藥物吸收代謝的規(guī)律。研究結(jié)果表明白藜蘆醇和FUDR的濃度在用五種給藥方法培養(yǎng)的線蟲體內(nèi)逐漸的升高,,在12-24小時(shí)達(dá)到最高,,并隨著培養(yǎng)時(shí)間的推移慢慢降低。同時(shí),,給藥的濃度越高,,線蟲代謝和外排越快。線蟲對(duì)低水溶性的白藜蘆醇和易溶于水的FUDR具有相似的吸收和代謝模式,。由于用于培養(yǎng)線蟲的培養(yǎng)基內(nèi)的藥物被活的細(xì)菌吸收,,導(dǎo)致培養(yǎng)基中藥物濃度降低較快,線蟲食用細(xì)菌為滅活狀態(tài)時(shí)要比食用細(xì)菌為存活狀態(tài)時(shí)的吸收效率高,。在五種培養(yǎng)方法中,,NGM dead method 和liquid growing method培養(yǎng)的線蟲吸收藥物的效率最高。線蟲體內(nèi)的藥物濃度可以換算為小鼠體內(nèi)的藥物劑量,,為線蟲給藥劑量和哺乳動(dòng)物給藥劑量之間的轉(zhuǎn)換提供了一個(gè)橋梁,。
上述研究結(jié)果以Drug Absorption Efficiency in Caenorhbditis elegans Delivered by Different Methods為題發(fā)表在《公共科學(xué)圖書館—綜合》(PLoS ONE)上。
該研究工作得到中國(guó)科學(xué)院百人計(jì)劃項(xiàng)目,、云南省高端科技人才項(xiàng)目,、植物化學(xué)與西部植物資源持續(xù)利用國(guó)家重點(diǎn)實(shí)驗(yàn)室項(xiàng)目的資助。(生物谷Bioon.com)
DOI:10.1371/journal.pone.0056877
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PMID:
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.