肾系疾病肝肾阴虚证血液代谢组学初探

Exploration on metabonomics of the kidney diseases of yin deficiency liver-kidney pattern

目的探讨常见肾系疾病中肝肾阴虚证的血液代谢组学异同,从小分子代谢水平方面探讨"同证异病"的客观物质基础及其与病、证的关系。方法以慢性肾衰竭、慢性肾炎、慢性泌尿系感染、糖尿病肾病4种疾病中辨证为肝肾阴虚证的患者为研究对象,采用超高效液相色谱-质谱(UPLC-MS)联用技术,对其血液样品进行代谢产物检测;采用偏最小二乘法-判别分析进行数据处理,获得样品的分类信息和不同于正常人的差异变量。将上述差异变量进行不同病理组间对照,得到共有和特有的差异变量,在HMDB数据库和Wiki Pathways数据库中进行比对检索,鉴定其特征代谢物及对应的代谢通路。结果肾系疾病肝肾阴虚证患者共有4个相同的代谢物不同于正常人,分别为2-(羟基亚氨基)-丙酸、L-同型半胱氨酸、十六酸和二鸟嘌呤核苷四磷酸;不同的特征代谢物共有57个,其中慢性肾衰竭18个,慢性肾炎16个,慢性泌尿系感染14个,糖尿病肾病9个。结论慢性肾系疾病中,中医"同证异病"的理论具有客观物质基础。相同证型有一致的物质基础(生物标志物);疾病不同,其对应的物质基础(生物标志物)有差异。"病""证"对患者的物质代谢均有影响,而"病"的影响可能大于"证"的影响。

Objective To explore the similarities and differences of the metabonomics of yin deficiency liver-kidney pattern among kidney diseases,and to discuss the objective material basis of＂ the same pattern in different diseases＂on small molecules metabolites and relationship between disease and pattern. Methods Ultra performance liquid chromatography- mass spectrum（ UPLC-MS） technology was adopted to test the blood metabolites on those with chronic kidney failure,chronic nephritis,chronic urinary tract infections and diabetic nephropathy of yin deficiency liver-kidney pattern. Meanwhile,partial-least-squares method was used to gain categorized statistics of the samples and difference variables by comparing that of healthy people. Common and unique difference variables were known by comparing of difference variables in each pathological group. The result was compared against the data in HMDB and Wiki Pathways database to identify those characteristic metabolites and corresponding metabolic pathways. Results Patients with kidney diseases of yin deficiency liver-kidney pattern share four metabolites which are different from healthy people,namely 2-（ hydroxyl diethanolamine）- Propionic acid,L- homocysteine,palmitic acid and Diguanosine tetraphosphate and 57 characteristic metabolites,among which 18 chronic kidney failure,16 chronic nephritis,14 chronic urinary tract infections and 9 diabetic nephropathy. Conclusion The theory of＂same pattern among different diseases＂is objective and fact-based in chronic renal diseases. The same syndrome could be traced to the consistent material basis（ biomarker）,while the different diseases to different material basis. ＂Diseases＂and＂pattern＂both have an impact on patients＇ metabolism,especially the＂diseases＂.