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肾虚证大鼠尿液的核磁共振谱代谢组学研究
高岗,杨根金,娄子洋*
0
(第二军医大学药学院药物分析测试中心,上海 200433)
摘要:
目的:应用1HNMR结合主成分分析(PCA)方法研究氢化可的松诱导的肾虚证大鼠和空白对照大鼠的尿液成分谱差异。方法:使用氢化可的松诱导大鼠建立肾虚证模型,1HNMR分析对照组和模型组大鼠的尿液,使用PCA方法进行模式识别,寻找标记物并做出相关代谢途径的可能解释。结果:PCA方法处理肾虚证和空白对照大鼠尿液数据显示,两组大鼠的数据可以在得分图实现分类,与对照组比较肾虚组大鼠由于氢化可的松诱导,大鼠机体进入一个过消耗后衰弱的状态,相关代谢发生显著变化,乳酸(δ 1.37)代谢发生堆积;二甲胺(δ 2.72)的含量增加,提示肾虚与肾功能异常是密切相关的;天冬氨酸(δ 2.83),牛磺酸(δ 3.44,3.28),马尿酸(δ 7.84,7.56,7.64,3.97),肌氨酸(δ 3.87)等的相对积分面积明显下降,这预示糖皮质激素可能引起了肾上腺皮质分泌功能的损害;琥珀酸(δ 2.41)和柠檬酸(δ 2.53,2.68)是三羧酸循环能量代谢及糖酵解的中间产物,其含量的降低,通常是由于线粒体功能紊乱所引起。结论:1HNMR结合PCA模式识别的代谢组学方法具有研究复杂条件下机体病理生理变化的优势,本研究为理解中医的肾虚证和为该类疾病临床诊治的研究提供了证据。
关键词:  代谢组学  磁共振波谱学  主成分分析  肾虚证  尿
DOI:10.3724/SP.J.1008.2009.0565
投稿时间:2008-10-20修订日期:2009-04-09
基金项目:
Metabonomic study on urine of rats with hydrocortisone-induced kidney deficiency syndrome
GAO Gang,YANG Gen-jin,LOU Zi-yang*
(Pharmaceutical Analysis Center,School of Pharmacy,Second Military Medical University,Shanghai 200433,China)
Abstract:
Objective:To apply 1HNMR spectroscopic analysis and principal components analysis(PCA) for investigating the fluctuation of metabolites between hydrocortisone-induced kidney deficiency syndrome(Shenxu Zheng) rats and the normal rats.Methods: Using 1HNMR based metabolic profiling and PCA,we investigated the difference of urine metabolites between the normal rats and rats with hydrocortisone-induced kidney deficiency syndrome.We also explained the changes of the related metabolic pathway or metabolic network.Results: The changes following hydrocortisone intervention of rats could be identified by PCA,and the kidney deficiency syndrome rats entered a state of “hyperfunction”,involving a series of changes in metabolic pathway and metabolic network.The response integral area of lactic acid(δ 1.37) increased,indicating the accumulation of metabolites of lactic acid.The amount of dimethylamine(δ 2.72) also increased,indicating that the disorder of kidney function was related to kidney-deficiency syndrome.The response of creatinine(δ 3.87),asparaginic acid(δ 2.83),taurine(δ 3.44,3.28),and hippurate(δ 7.84,7.56,7.64,3.97) all decreased significantly,indicating that the hydrocortisone might cause adrenal cortex excretion injury.The response integral area of succinate(δ 2.41) and citric acid(δ 2.53,2.68) decreased,which was usually caused by disorder of the mitochondrial function.Conclusion: It is suggested that the metabonomic approach can be used to investigate the pathophysiological changes under certain physiopathologic conditions.This study provides evidence for understanding “Shenxu Zheng”(kidney deficiency syndrome) in traditional Chinese medicine and for diagnosis and therapy of such diseases.
Key words:  metabonomic  magnetic resonance spectroscopy  principal components analysis  kidney deficiency syndrome  urine