膝骨关节炎肝肾亏虚证与寒湿痹阻证的血浆代谢组学差异研究

Study on the Difference of Plasma Metabolomics Between Liver and Kidney Deficiency Syndrome and Cold-Dampness Bi Syndrome in Knee Osteoarthritis

目的研究膝骨关节炎(knee osteoarthritis, KOA)肝肾亏虚证与寒湿痹阻证的差异代谢物,探讨KOA肝肾亏虚证与寒湿痹阻证辨证差异的物质代谢轮廓。方法选取KOA肝肾亏虚证和寒湿痹阻证患者各30例,采用核磁共振氢谱(~1H nuclear magnetic resonance spectroscopy,~1H-NMR)技术测定血浆中的小分子代谢物,采用主成分分析法和正交偏最小二乘法-判别分析,进行多元统计分析。结果肝肾亏虚组与寒湿痹阻组血浆样本有5个差异代谢物有统计学意义(P<0.05),其中高密度脂蛋白、柠檬酸、低密度脂蛋白/极低密度脂蛋白在肝肾亏虚组患者中含量明显高于寒湿痹阻组患者,而醋酸、组氨酸含量明显低于寒湿痹阻组患者。依富集程度(P<0.05)判别代谢通路为乙醛酸和二羟酸代谢、组氨酸代谢、柠檬酸循环、β-丙氨酸代谢、丙酮酸代谢、糖酵解和糖异生。结论KOA肝肾亏虚证和寒湿痹阻证患者存在差异代谢物,分型的差异代谢物质基础可能是柠檬酸盐、组氨酸和醋酸。其中醋酸、组氨酸可能为寒湿痹阻证的标志性代谢产物。

Objective To study the difference of metabolites between liver-kidney deficiency syndrome and cold-dampness Bi syndrome in knee osteoarthritis(KOA),and to explore the material metabolism profile of the difference between liver-kidney deficiency syndrome and cold-dampness Bi syndrome in KOA.Methods The plasma of 30 KOA patients with liver and kidney deficiency syndrome and cold-dampness Bi syndrome were collected.1H nuclear magnetic resonance spectroscopy(1H-NMR)technology was applied to determine small molecule metabolites in plasma.Principal component analysis and partial least squares discrimination analysis were performed to conduct multivariate statistical analysis.Results There were 5 different metabolites in the plasma samples of liver and kidney deficiency group and cold-dampness Bi group,with statistical significance(P<0.05).The contents of high density lipoprotein(HDL),citrate and low density lipoprotein(LDL)/very low density lipoprotein(VLDL)in patients with liver-kidney deficiency group were significantly higher than those in patients with cold-dampness Bi group,while the contents of acetate and histidine were significantly lower than those in patients with cold-dampness Bi group.According to the enrichment degree(P<0.05),the metabolic pathway was identified as glyoxylate and dicarboxylate metabolism,histidine metabolism,citrate cycle,β-alanine,pyruvate metabolism,glycolysis/gluconeogenesis.Conclusion There are different metabolites in KOA patients with liver and kidney deficiency syndrome and cold-dampness Bi syndrome.Citrate,histidine and acetate may be the different metabolites of syndrome type.Acetate and histidine may be the iconic metabolites of cold-dampness Bi syndrome.