从代谢组学角度初探中医“虚证”证候模型评价指标的建立  

Exploration on the establishment of the evaluation system of'deficiency syndrome'from the perspective of metabolomics

作　　者：西旺 宋楠楠[1] 闫起 王燕[1] 徐静[1] 李奇玮[1] 梁华[1] XI Wang;SONG Nan-nan;YAN Qi;WANG Yan;XU Jing;LI Qi-wei;LIANG Hua(Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,哈尔滨150040

出　　处：《中华中医药杂志》2020年第5期2234-2239,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81473563);国家重点基础研究发展计划(973计划)(No.2013CB531801)。

摘　　要：目的:通过代谢组学的研究方法,观察机能衰退的老年小鼠在经过补气(四君子汤)、补血(四物汤)、补阴(六味地黄汤)、补阳(金匮肾气汤)的治疗后,机体的内源性代谢变化,以方测证总结出气、血、阴、阳亏虚有关的标志物,从而为建立"虚证"证候模型的多组学评价指标打下基础。方法:以16月龄自然衰老小鼠作为研究对象,同时设立3月龄小鼠为青年组。经过经典补益方剂治疗后,采取UPLC-Q-TOF-MS技术对血浆样本进行检测,采用主成分分析法(PCA)和正交偏最小二乘-判别分析法(OPLS-DA),最终归纳出与"虚证"证候密切相关的代谢物指标。结果:通过补气治疗后,小鼠血浆中L-天冬氨酰-4-磷酸、癸酸、萨索林-1-羧酸盐、没食子酸、L-二氢乳清酸、二十二碳六烯酸的表达水平明显回调,向3月龄小鼠靠拢。补血可以改善DL-O-磷酸丝氨酸、磷酸高丝氨酸、硬脂醛等10种标志物的表达水平。补阳可以改善左旋肉碱、脱氧腺苷、没食子酸的表达水平;补阴后血浆中花生酸、没食子酸、硫酸苯酚等6种标志物出现良性调整(P≤0.05)。结论:每种虚证证候都存在特异性的代谢标志物,气虚证可以影响机体内癸酸等6种代谢物的表达,血虚证可以影响硬脂醛等10种代谢物,阳虚证可影响左旋肉碱等3种代谢物,阴虚证可影响硫酸苯酚等6种代谢物,这为中医"虚证"证候模型的多组学研究提供了生物学依据。Objective: Through the method of metabolomics, the aging mice with hypothetical dysfunction were treatment with tonifying qi(Sijunzi Decoction), enriching bloodl(Siwu Decoction), tonifying yin(Liuwei Dihuang), tonifying yang(Jingui Shenqi Decoction). After treatment, the endogenous changes of the body, the side of the test to summarize the qi, blood, yin, yang deficiency and related metabolic markers, syndrome detecting from formula used, thus laying the foundation for the multi-omics evaluation system of ‘deficiency syndrome’ syndrome. Methods: The 16-month-old natural aging mice were used as research subjects, and 3 months old mice were established as young groups. After the treatment with the classic tonic prescription, UPLC-QTOF-MS technique was used to detect the plasma samples, using principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) analysis. Metabolic markers closely related to the syndrome of ’deficiency syndrome’. Results: After treatment with tonifying qi, the expression levels of L-Aspartyl-4-phosphate, capric acid, salsoline-1-carboxylate, gallic acid, L-dihydrowhey acid and docosahexaenoic acid in the plasma of mice were obvious. Callback, close to 3-month-old mice. Blood supplementation could improve the expression levels of 10 markers such as DL-O-phosphoserine, phosphohomoserine, and stearyl etc.. Supplementary yang could improve the expression level of L-carnitine, deoxyadenosine and gallic acid;after supplement yin, the plasma has a benign adjustment of 6 markers such as arachidic acid, gallic acid and phenol sulfate, etc.(P≤0.05). Conclusion: Each type of deficiency syndrome has specific metabolic markers. Qi deficiency syndrome can affect the expression of 6 metabolites such as capric acid in the body, blood deficiency syndrome can affect 10 metabolites such as stearyl, and yang deficiency syndrome can affect L-carnitine and other 3 metabolites, yin deficiency syndrome can affect 6 metabolites, such as phenol sulfate. This provides

关 键 词：虚证 证候模型 组学 代谢组学 评价指标 以方测证 代谢标志物 

分 类 号：R255[医药卫生—中医内科学]