基于液相色谱与质谱联用技术的良性前列腺肥大小鼠血清代谢组学分析

摘要

良性前列腺肥大已成为影响老龄男性生活质量的一个常见因素，其发病机制迄今尚未完全阐明。本研究采用超高压液相色谱-四极杆飞行时间串联质谱（ UPLC-QTOF-MS）技术检测正常小鼠、良性前列腺肥大和非那雄胺干预的模型小鼠血清中代谢物的变化，对3组小鼠的血清代谢谱进行了分析。采用偏最小二乘-判别分析（ PLS-DA）对3组小鼠代谢物分类并寻找潜在生物标志物。数据显示，3组小鼠的血清代谢物谱得到了很好的区分，发现并鉴定了3个潜在生物标志物，分别为1-棕榈酰溶血磷脂酰胆碱、1-O-十六烷基-2-O-乙酰基-SN-甘油基-3-磷酸胆碱和（ Z）-13-二十二烯酰胺。结果表明良性前列腺肥大的发生与脂质代谢紊乱密切相关。%Benign prostatic hyperplasia( BPH)increasingly becomes a common factor affecting the quality of life of aging men. Its pathogenesis has not yet been fully elucidated. Ultra-high pressure liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-QTOF-MS) was employed to detect the changes of serum metabolites in normal mice,benign prostatic hyperplasia model mice and BPH model mice with finasteride intervention. The serum metabo-lite profiles of the three groups of mice were analyzed. Partial least squares-discriminant analy-sis( PLS-DA)was used for group differentiation and biomarker selection. The results showed good distinction among the three groups of mice serum metabolite spectra. Three potential bio-markers, 1-hexadecanoyl-SN-glycero-3-phosphocholine, 1-O-hexadecyl-2-O-acetyl-sn-glyceryl-3-phosphorylcholine and( Z)-13-docosenamide,were discovered and identified. They all indica-ted the occurrence of benign prostatic hypertrophy is closely related to the disorders of lipid metabolism. Compared with the control group,the contents of the first two substances were significantly increased in the serum of BPH model mice,and significantly decreased after inter-vened by finasteride. The contents of( Z)-13-docosenamide decreased significantly in the serum of model group, and increased after intervened by finasteride. Compared with the control group,the contents of three biomarkers in finasteride group did not recover completely and had significant differences. This study is conductive to open new avenues of diagnosis and medical treatment for BPH.