基于代谢组学技术分析四物汤治疗原发性痛经证的作用机制  

Analysis of Therapeutic Mechanism of Siwutang in Primary Dysmenorrhea Syndrome Based on Metabolomics Technique

作　　者：何瑶[1] 王丽娟[1] 刘婷婷[1] 陈哲杰[1] 傅超美[1] 刘盈[1] 

机构地区：[1]成都中医药大学药学院,成都611137

出　　处：《中国实验方剂学杂志》2017年第12期82-89,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金青年项目(81303238)

摘　　要：目的:从内源性代谢物的角度研究四物汤治疗原发性痛经证的作用机制。方法:构建苯甲酸雌二醇-缩宫素联用致大鼠痛经模型;采用UPLC-Q-TOF-MS技术分析痛经大鼠血浆中代谢物的指纹图谱,电喷雾正离子模式(ESI+)和负离子模式(ESI-)对样品进行检测,m/z 50~1 000,结合质谱信息和公共数据库检索对检测到的代谢物进行鉴定;运用主成分分析(PCA)和偏最小二乘法判别分析(PLS-DA)筛选正常组、痛经模型组和四物汤组之间的差异代谢物;对差异代谢物进行KEGG(京都基因与基因组百科全书)代谢通路分析。结果:痛经模型大鼠中检测鉴定23种内源性代谢产物;其中痛经模型组与正常组相比,黄体酮,11-脱氧皮甾醇,牛磺熊去氧胆酸和溶血磷脂酸为差异代谢物[变量重要性投影值(VIP)>1,P<0.05]。四物汤组与痛经模型组相比,L-苯丙氨酸,L-酪氨酸,N-苯甲酰甘氨酸,L-蛋氨酸,11-脱氧皮甾醇和硬脂酸甘氨酰胺为差异代谢产物(VIP>1,P<0.05)。结论:四物汤对原发性痛经证大鼠体内差异代谢物有一定的回调作用,其作用机制主要与影响类固醇激合成、溶血磷脂酸代谢、氨基酸代谢相关。Objective： To study on the mechanism of Siwutang in treating primary dysmenorrhea syndrome from the aspect of endogenous metabolites. Method： Dysmenorrhea rat model was constructed by injecting estradiol benzoate and oxytocin. UPLC-Q-TOF-MS was employed to analyze fingerprint of metabolites in plasma of dysmenorrhea rats under electrospray ionization positive and negative ion mode, the acquired metabolites were identified by mass spectrum informations and public database retrieval. Principal component analysis （PCA） and partial least squares discriminant analysis （PLS-DA） were adopted to screen the differential metabolites among the normal group, dysmenorrhea model group and Siwutang group; these different metabolites among three groups were analyzed by KEGG metabolic pathway method. Result： Twenty-three endogenous metabolites from dysmenorrhea model rats were detected and identified; when the dysmenorrhea model group compared with the normal group, progesterone, cortexolone, tauroursodeoxycholic acid and lysophosphatidic acid were the different metabolites with variable importance in the projection （VIP） 〉 1 and P 〈 0.05. When the Siwutang group compared with the model group, L-phenylalanine, L-tyrosine, N-benzoylglycine, L-methionine, cortexolone and stearic acid glycinamide were the different metabolites with VIP 〉 1 and P 〈 0.05. Conclusion： Siwutang has a certain callback effect on the differential metabolites in primary dysmenorrhea rats, its therapeutic mechanism is mainly related to steroid synthesis, lysophosphatidie acid metabolism and amino acid metabolism.

关 键 词：四物汤 代谢组学 原发性痛经 主成分分析 11-脱氧皮甾醇 溶血磷脂酸 L-酪氨酸 

分 类 号：R969[医药卫生—药理学] R945[医药卫生—药学]