基于代谢组学技术的烟酰胺协同两性霉素B抑制白念珠菌的作用机制研究
投稿时间:2023-07-17  修订日期:2023-12-31  点此下载全文
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作者单位邮编
万立志 海军军医大学 200433
王境焓 海军军医大学 200433
吴春蓉 海军军医大学 200433
李玲 海军军医大学 200433
基金项目:国家自然科学基金(82104127)
中文摘要:目的:基于代谢组学的方法研究烟酰胺协同两性霉素B抑制白念珠菌的潜在作用机制。 方法:用适当浓度的烟酰胺、两性霉素B以及二者联用处理浮游型白念珠菌,基于气相色谱-质谱联用技术分析其胞内代谢物,通过多元统计分析筛选差异代谢物,并用NIST数据库进行检索鉴定。 结果:与空白对照组相比,烟酰胺单独干预组与之分离趋势不明显,而两性霉素B组、联用组与之具有明显的分离趋势。两性霉素B干预后有23个代谢物发生显著性变化,烟酰胺和两性霉素B联合干预后有28个代谢物发生显著性变化,包括氨基酸,有机酸,多胺,糖类等成分。结论:烟酰胺作为白念珠菌的内源性谢物,与AmB联用后,增强AmB在原本代谢通路中的作用,同时在也一定程度上改变了其作用途径,推测NAM与AmB后可能通过调整白念珠菌的三羧酸循环,干扰其氨基酸代谢,影响多胺的合成等途径,发挥其对AmB的增效作用。
中文关键词:气相色谱-质谱联用,两性霉素B,烟酰胺,白念珠菌,代谢组学
 
The mechanism of nicotinamide combined with amphotericin B against Candida albicans based on metabolomics technology
Abstract:Objective: To investigate the potential mechanism of nicotinamide combined with amphotericin B against Candida albicans based on metabolomics. Methods: The intracellular metabolites of C. albicans intervened by different drμgs were analyzed by gas chromatography-mass spectrometry. The differential metabolites were screened by multivariate statistical analysis and identified by searching the NIST database. Results: Compared with the blank control group, the nicotinamide intervention group had no obvious separation trend, while the amphotericin B and combined treatment groups had obvious separation trend. After amphotericin B intervention, 23 metabolites were significantly changed, and 28 metabolites were significantly changed after combined intervention, including amino acids, organic acids, sugars and other components. Conclusion: Nicotinamide, as an endogenous metabolite of C. albicans, combined with amphotericin B can significantly enhance the role of AmB in the original metabolic pathway and changed it to a certain extent. It is speculated that AmB combined with NAM may pose more antibacterial effect on Candida albicans by regulating the tricarboxylic acid cycle,interfering with amino acid metabolism and influencing polyamine synthesis.
keywords:Gas chromatography-mass spectrometry, Amphotericin B, Nicotinamide, Candida albicans, Metabolomics
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