基于^(1)H-NMR代谢组学的绝经期综合征血清代谢标志物研究

Research on serum metabolic markers of menopausal syndrome based on^(1)H-NMR metabolomics

目的:基于核磁共振氢谱(1H-NMR)代谢组学分析,结合模式识别寻找女性进入围绝经期以及罹患绝经综合征疾病的特异性血清代谢标志物。方法:选择80例绝经综合征患者、40例同龄围绝经期和40例育龄期健康女性为对照,利用^(1)H-NMR技术进行血清样本检测,运用PLS-DA、OPLS-DA分析对体内代谢产物进行比较研究。结果:绝经综合征患者与围绝经期、育龄期健康女性三组之间具有统计学差异的血清代谢物包括:乳酸、醋酸、谷氨酸、丙酮酸、肌酸、氧化三甲胺(TMAO)、N-乙酰糖蛋白、丙氨酸和胆碱。其中,进入围绝经期的健康女性,较育龄期有乳酸、醋酸等6个血清代谢产物显著下调,但尚不具备诊断价值。与围绝经期健康女性比较,绝经综合征患者丙氨酸、TMAO上调,谷氨酸、丙酮酸、N-乙酰糖蛋白和胆碱下调趋势显著,且谷氨酸、丙酮酸、N-乙酰糖蛋白和胆碱的变化趋势具有一定的诊断价值。结论:围绝经期是女性从生殖期过渡到老年期的一个特殊生理阶段,健康女性虽然较育龄期存在一定特征性代谢物的变化,但尚不具有诊断价值;但绝经综合征患者在疾病状态下所呈现的差异性代谢标志物,具有一定的诊断价值,可以为临床宏微观结合诊断绝经综合征提供一定的客观依据。

AIM:To find specific metabolic markers for women entering peri-menopausal period and patients with menopausal syndrome based on^(1)H-NMR metabolism serum metabolite analysis combined with pattern recognition.METHODS:Eighty patients with menopausal syndrome,40 peri-menopausal women of the same age and 40 healthy women of childbearing age as controls were selected.Then the serum samples were detected by nuclear magnetic resonance spectroscopy(^(1)H-NMR),and the metabolites were compared by partial least square discriminant analysis(PLSDA)and orthogonal partial least square discriminant analysis(OPLS-DA).RESULTS:There were nine serum metabolites with significant differences among the three groups of menopausal syndrome patients and the healthy women during the perimenopausal and childbearing period,which include lactic acid,acetic acid,glutamic acid,pyruvate,creatine,TMAO,N-acetylglycoprotein,alanine and choline.Compared with the healthy women of childbearing age,there were six serum metabolites of menopausal syndrome decreased significantly,but they had no diagnostic value yet.Compared with the healthy peri-menopausal women,the contents of alanine and TMAO were significantly increased,while the contents of glutamate,pyruvate,N-acetylglycoprotein and choline were significantly decreased in patients with menopausal syndrome.And the changes of glutamic acid,pyruvic acid,Nacetylglycoprotein and choline had certain diagnostic value.CONCLUSION:Peri-menopausal period is a special physiological stage of women's transition from reproductive period to old age.Though healthy women have some changes compared with childbearing age,they do not have diagnostic value.However,the differential metabolic markers in patients with menopausal syndrome have a certain diagnostic value,which can provide a certain objective basis for the clinical diagnosis of menopausal syndrome.