基于超高效液相色谱-质谱分析的代谢组学在小檗碱治疗多囊卵巢综合征研究中的应用  

Application of metabolomics in treating polycystic ovary syndrome with berberine based on ultra high performance liquid chromatography-mass spectrometry

作　　者：李艳杰[1] 张春兰[2] 张晗[3] 赵欣捷[1] 侯丽辉[2] 许国旺[1] 

机构地区：[1]中国科学院分离分析化学重点实验室中国科学院大连化学物理研究所,辽宁大连116023 [2]黑龙江中医药大学附属第一医院妇产科,黑龙江哈尔滨150040 [3]天津中医药大学第一附属医院妇科,天津300193

出　　处：《色谱》2014年第5期464-471,共8页Chinese Journal of Chromatography

基　　金：黑龙江省科技攻关项目(GC10C217)

摘　　要：多囊卵巢综合征(polycystic ovary syndrome,PCOS)是妇女最常见的内分泌和代谢紊乱性疾病,合理的药物治疗非常重要。本研究中,超重/肥胖的多囊卵巢综合征患者经过小檗碱治疗3个月,采集治疗前后的血样进行分析,利用超高效液相色谱-质谱联用技术(UHPLC-MS)对治疗前后血清中的内源性物质进行了相对含量测定。正交信号校正的偏最小二乘模式识别分析结果显示治疗前后有明显的区分。多变量分析结合非参数检验找出的与小檗碱治疗相关的差异代谢物均与脂类代谢有关。临床生化数据结合代谢组学数据显示,小檗碱治疗超重/肥胖型的多囊卵巢综合征患者可以增加机体胰岛素敏感性、改善脂类代谢。上述研究结果表明代谢组学是研究中药治疗疾病效果的有效工具之一。Polycystic ovary syndrome（ PCOS）is a complex,heterogeneous disorder,which seriously impacts the health of reproductive age women. Thus reasonable individual-based treat-ment is important. In this study,the serum samples of 15 overweight PCOS patients before and after treatment with berberine for three months were collected for clinic biochemical test and metabolomic research. Metabolomic profiling based on ultra high performance liquid chromatog-raphy（ UHPLC）coupled with quadrupole time-of-flight mass spectrometry（ q-TOF MS）was used to investigate metabolic changes of PCOS. Compared with before treatment,the patients after berberine treatment can be separated into distinct clusters as displayed by the orthogonal signal correction partial least-squares discriminant analysis （ OSC-PLS-DA ） score plot with model parameter：R2Y=0. 892,Q2（cum）= 0. 577,which indicated changes in metabolites after berberine treatment. The differential metabolites related to berberine treatment were selected when their variable importance values were more than 1,and p﹤0. 05 with nonparametric test. These differential metabolites were all involved in lipids metabolism ,including phosphatidyl-cholines,sphingomyelin,stearic acid and erucamide. The pharmacological results and metabo-lomic data revealed that berberine can strengthen the sensitivity of insulin and rectify the dyslip-idemia of overweight PCOS patients. This study also illustrates that the LC-MS based metabolo-mic method is helpful for evaluating the treatment of traditional Chinese medicines.

关 键 词：超高效液相色谱-质谱联用 代谢组学 小檗碱 多囊卵巢综合征 ultra high performance liquid chromatography-mass spectrometry( UHPLC-MS) 

分 类 号：O658[理学—分析化学]