蛇麻酮对结核分枝杆菌转录组诱导的高通量分析.docVIP

  蛇麻酮对结核分枝杆菌转录组诱导的 高通量分析# 梁俊超1，唐旭东2，于录1** 5 10 15 20 25 30 35 40 （1. 吉林大学人兽共患病研究所，人兽共患病研究教育部重点实验室，长春 130062； 2. 深圳清华大学研究院，广东 深圳 518057） 摘要：目的：揭示蛇麻酮抗结核分枝杆菌的潜在作用机制。方法：通过药物敏感性试验测定 蛇麻酮的最低抑菌浓度，利用商业寡核苷酸芯片分析经亚抑菌浓度蛇麻酮处理后结核分枝杆 菌全基因组转录水平的变化，选择部分基因进行实时定量 RT-PCR 实验，用于验证基因芯片 结果。结果：蛇麻酮的最低抑菌浓度 10 ug/ml, 经蛇麻酮作用后共有 540 个基因发生显著 差异变达。其中，254 个基因上调，286 个基因下调。一些涉及重要通路的基因被显著调节， 例如细胞色素 P450 酶系统、PE/PPE 多基因家族、表面暴露脂质合成通路、ABC 转运蛋白及 蛋白合成通路。结论：蛇麻酮具有较好的抗分枝杆菌活性, 能影响大量结核分枝杆菌不同通 路的重要基因，本研究对蛇麻酮抗结核分枝杆菌作用机制的研究具有重要意义。 关键词：结核分枝杆菌；蛇麻酮；寡核苷酸基因芯片 中图分类号：S432.4+2 文献标识码：A Genome-wide transcription analyses in Mycobacterium tuberculosis treated with lupulone Liang Junchao1, Tang Xudong2, Yu Lu1 (1. Key Laboratory of Zoonosis Research, Ministry of Education, ChangChun 130062,; 2. Key Lab for New Drug Research of TCM, Research Institute of Tsinghua University in Shenzhen, GuangDong ShenZhen 518057) Abstract: Aim：To reveal the possible mechanism of action of lupulone against Mycobacterium tuberculosis (M. tuberculosis). Methods: Commercial oligonucleotide microarrays were used to analyze the genome-wide transcriptional changes triggered by treatment with minimal inhibitory concentration (MIC) of lupulone. Quantitative real-time RT-PCR was performed for selected genes to verify the microarray results. We interpreted our microarray data using Agilent software. Results: Analysis of the microarray data revealed that a total of 540 genes were differentially regulated by lupulone. Of these, 254 genes were upregulated, and 286 genes were downregulated. Some of the important genes that were significantly regulated are related to different pathways (such as surface-exposed lipids, cytochrome P450 enzymes, PE/PPE multigene families, ABC transporters, and protein synthesis). Conclusion：Our results showed that lupulone has potential antimycobacterial activity and our DNA microarray analysis demonstrated that lupulone affected a number of important genes involved in different pathways in M. tuberculosis. These findings may