个体化评价下不同人群六味地黄胶囊体内代谢过程差异比较研究

Difference Comparison of Liuwei Dihuang Capsule in vivo Metabolic Process in Different Populations after Individualized Evaluation

目的:在前期研究的临床个体化评价基础上,进一步采用代谢组学研究六味地黄胶囊在健康人、临床评价有效受试者、临床评价无效受试者的指纹图谱差异,为中药个体化评价方法的推广提供试验依据,并试图发现六味地黄胶囊治疗肾阴虚证的相关生物标志物。方法:选择健康受试者、单病例随机对照评价有效者和无效者,给予连续服用六味地黄胶囊3 d,采用液质联用测定结合模式识别方法分析3组人群服药后的代谢产物差异。结果:3组人群血浆样品正、负离子扫描总离子流色谱图未发现明显不同,进一步数据分析筛选的生物标记物提示3组人群服用六味地黄胶囊后其生理代谢受到干扰,并存在一定差异。研究将所得的生物标记物用自建的六味地黄胶囊代谢库进行检索,没能发现相同离子,说明所得到的标志物均为内源性物质。结论:3组人群服药后代谢差异印证了单病例随机对照评价证候类中药的可行性,肾阴虚证的生物标志物及六味地黄胶囊对其的影响仍需大量实验研究。

Objective ： In order to provide experiment basis to promote individualized evaluation method, and to discover biomarkers of kidney Yin deficiency syndrome, we evaluated the difference of Liuwei Dihuang Capsule fingerprint in healthy subject, clinical evaluation of effective subjects, clinical evaluation of invalid subjects, on the bases of previous individualized evaluation. Methods： Healthy subjects, clinical evaluation of effective subjects, and clinical evaluation of invalid subjects were given Liuwei Dihuang Capsule continuously for 3 days, the metabolite differences after taking medicine were analyzed with LCMS technology and pattern recognition method. Results ： Plasma total ions ehromatogram of three groups of people showed no significant different. Screened biomarkers after further data analysis suggested that physiological metabolism of three groups of people were disturbed and different. We retrieved the biomarkers using self-built metabolic library of Liuwei Dihuang Capsule, found that there was no same ion, which showed that the biomarkers are endogenous substances. Conlusion ： The difference of metabolites between three groups confirmed the feasibility of n-of-1 RCT in clinical evaluation of TCM drugs used for syndromes. The biomarkers of kidney Yin deficiency and impact of Liuwei Dihuang Capsule needs a lot of experimental research.