目的 利用代谢组学技术探讨大黄治疗慢性肾功能衰竭(CRF)的作用机制。 方法 采用腺嘌呤制备大鼠CRF模型, 以高分离度快速液相色谱-质谱(RRLC-MS)为核心分析技术, 以主成分分析法为数据解析手段, 筛选出CRF特征性内源代谢产物, 探讨大黄治疗CRF的作用机制。 结果 大黄能减弱或取消外界刺激因素(如腺嘌呤)诱发CRF, 且对其代谢轨迹的扰动具明显的回调作用, 其作用机制可能与潜在生物标志物有关。 结论 大黄通过减少CRF大鼠血液中儿茶酚胺类物质生成、磷酸酯类物质分解、炎症介质产生, 使体内D-谷氨酰胺、D-谷氨酸代谢和蛋氨酸循环恢复正常而发挥治疗CRF的作用。

Objective To explore the mechanism of Rheum officinale in the treatment of chronic renal failure (CRF) based on metabolomics. Methods CRF model of rats was established using adenine. An RRLC-MS method was used for analysis and the data were processed by PCA to acquire characteristic endogenous metabolites and to investigate the mechanism of R. officinale on CRF. Results R.officinale weakened or eliminated the induction of CRF in rats, like adenine, helped obviously normalize the metabolome in rats, which might be associated with the potential biomarkers. Conclusion R.officinale could cure CRF through decreasing the synthesis of catecholamines compounds, decomposition of phosphate ester compounds, and production of inflammatory mediators in blood and making D-glutamine, D-glutamic acid metabolism, and methionine cycle back to normal.

国家自然科学基金资助项目(81001689)；国家中医药管理局中医药科学技术研究专项(06-07JP38)