| 利用酵母模型研究化合物对青蒿素作用的影响 | |
| 龙贡波 ; 孙辰 ; 李坚 ; 曹玉 ; 周兵 ; LONG Gong-bo ; SUN Chen ; LI Jian ; CAO Yu ; ZHOU Bing | |
| 2016-03-30 ; 2016-03-30 | |
| 关键词 | 青蒿素 铁 解偶联剂 线粒体 酵母 Deficit irrigation 0-1 programming Farmland water balance Crop water production function R285 |
| 其他题名 | Effects of various compounds on efficacy of artemisinin in a yeast model |
| 中文摘要 | 青蒿素类药物在疟疾治疗过程中有着非常重要的作用,且应用多年来尚鲜有真正临床抗药性的病例报道。世界卫生组织推行青蒿素联合疗法,旨在增强青蒿素的药效以及防止耐药病原株的出现。课题借助酵母这一经典模式生物,基于目前已知的青蒿素作用机制和相关理论假说,挑选部分化合物探究其与青蒿素的相互作用,旨在发现能调节青蒿素药效的化合物,并为青蒿素作用机制的研究及临床用药提供参考。实验涉及了氧化剂,抗氧化剂,金属离子,金属螯合剂,解偶联剂等,即将酿酒酵母菌株BY4742在同时含4μmol·L-1青蒿素与一定浓度化合物的非发酵固体培养基YPGE中30℃培养48h,通过观察其生长状态来评价化合物对青蒿素药效的影响。研究结果表明0.2 mmol·L-1Fe Cl3,60μmol·L-1BPS,1 mmol·L-1Cu Cl2,0.75 mmol·L-1VE和1 mmol·L-1VC对青蒿素有拮抗作用,40μmol·L-1DNP,0.1μmol·L-1CCCP和0.25 mmol·L-1H2O2与青蒿素之间存在协同作用。这些结果进一步支持了本实验室先前提出的青蒿素线粒体作用模型,提示改变细胞内氧化还原水平或者导致线粒体功能障碍的化合物会影响青蒿素药效的发挥,该研究同时也为青蒿素联合用药提供了一种简便的筛选方法。; Artemisinin is a key anti-malarial drug and few clinically meaningful resistant cases about its application have so far been reported. The World Health Organization( WHO) officially recommended the use of ACT( Artemisinin-based Combination Therapy) as the first line antimalarial application to increase its inhibitory efficacy and prevent the likely resistance development. Based on our current understanding of artemisinin,a set of compounds were selected to study their interaction with artemisinin by using the yeast( S. cerevisiae) model,in the hope that knowledge gained might provide some references for clinical investigations. In this research,yeast strain( BY4742) was cultured in the nonfermentable YPGE solid medium with 4 μmol·L- 1artemisinin and one of the selected compounds for 48 hours,and the combined drug efficiency was evaluated by the inhibition of yeast growth. The compounds belong to the categories of oxygenants,antioxidants,metal ions,ion chelators and uncouplers. Among them,0. 2 mmol·L- 1Fe Cl3,60 μmol·L- 1BPS,1 mmol·L- 1Cu Cl2,0. 75 mmol·L- 1VE and 1 mmol·L- 1VC antagonized the action of artemisinin,while 40 μmol·L- 1DNP,0. 1 μmol·L- 1CCCP and 0. 25 mmol· L- 1H2O2 had synergistic effects. These results suggested that redox-active and mitochondria-dysfunctional compounds could affect artemisinin' s potency,supporting our prior proposed mitochondrial model for artemisinin's action. This research in addition provided a convenient method to screen likely artemisinin-interacting compounds. |
| 语种 | 中文 ; 中文 |
| 内容类型 | 期刊论文 |
| 源URL | [http://ir.lib.tsinghua.edu.cn/ir/item.do?handle=123456789/148488]  |
| 专题 | 清华大学 |
| 推荐引用方式 GB/T 7714 | 龙贡波,孙辰,李坚,等. 利用酵母模型研究化合物对青蒿素作用的影响[J],2016, 2016. |
| APA | 龙贡波.,孙辰.,李坚.,曹玉.,周兵.,...&ZHOU Bing.(2016).利用酵母模型研究化合物对青蒿素作用的影响.. |
| MLA | 龙贡波,et al."利用酵母模型研究化合物对青蒿素作用的影响".(2016). |
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