代谢组学研究甲硝唑对高脂血症金黄地鼠机体代谢的影响  

Effect of metronidazole on metabolism of hyperlipidaemia hamster studied by metabonomics

作　　者：顾胜华[1] 阿基业[1] 査伟斌[1] 王广基[1] 吴晓磊[2] 刘林生[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室,南京210009 [2]北京大学工学院,北京100190

出　　处：《中国药科大学学报》2012年第5期443-448,共6页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81072692);国家重点基础研究发展计划("九七三"计划)资助项目(No.2011CB505303)~~

摘　　要：以基于气相色谱/飞行时间质谱(GC-TOF/MS)检测技术的代谢组学方法为技术手段,研究甲硝唑给药对高脂血症金黄地鼠整体代谢的调节作用,并采用末端限制性酶切片段长度多态性(T-RFLP)技术研究甲硝唑对金黄地鼠肠道菌群构成所造成的影响。研究发现高脂血症模型动物血脂升高,并存在明显的体内代谢和肠道菌群的紊乱。连续给予金黄地鼠灌胃二周甲硝唑后有较好的降脂作用,并能部分改善金黄地鼠因高脂饲料引起的代谢组学的和肠道菌群紊乱。但是,甲硝唑同时也可干扰机体的代谢,并能引起肠道正常菌群的紊乱,将其作为一个新型降脂药物应用于临床需进一步研究。Gas chromatography/Time-of-Flight mass spectrometry （GC/TOF-MS） based metabonomic studies were undertaken to investigate the in vivo metabolic variations caused by metronidazole treatment in hyperlipi- demia hamster. Terminal restriction fragment length polymorphism （T-RFLP） was used to investigate the composi- tion of gut microbiota of hamster. Obvious metabolic and gut microbiota disorders were observed in the model hamsters. After treatment with metronidazole, the lipid metabolism was regulated towards normal level. Moreover, the intragastric administration of metronidazole reversed part of gut microbiota disturbed by high fat diet. However, oral- administered metronidazole can also perturb other metabolites as well as normal gut flora of hamster. The results remind us that the perturbation of metabolism should be paid attention to before the application of metronidazole as a hypolipidemic agent.

关 键 词：代谢组学 气相色谱-飞行时间质谱 甲硝唑 肠道菌群 降血脂药 

分 类 号：R969.1[医药卫生—药理学]