慢性心力衰竭中医证候生物学诊断模式及代谢组学研究
|
摘要
慢性心力衰竭中医证候生物学诊断模式及代谢组学研究
研究目的
探讨慢性心衰证候分布组合特点及影响因素,对慢性心衰患者进行多项生物学指标检测和代谢组学核磁波谱分析,将一般统计学方法与数据挖掘方法相结合,在宏观和微观层面挖掘与疾病及证候相关的代谢物,并与代谢路径结合,提取敏感性和特异性强的证候特征指标群,为慢性心衰证候客观化诊断及中药复方干预提供参考依据。研究方法
1.临床横断面研究：全面采集630例慢性心衰患者人口学资料、现病史信息、中医四诊信息及诊断结果,对证候属性进行判别,描述慢性心衰证候分布特点和组合规律并对影响因素进行Logistic回归分析。
2.慢性心衰证候生物学诊断模式研究：检测符合纳入标准的100例慢性心衰患者临床生化指标及超声心动图结果,运用数据挖掘方法对各证候生物学指标进行相关分析和特征提取,在此基础上用神经感知器方法构建各证候生物学诊断模式。
3.慢性心衰患者血浆代谢组学研究：对比46例冠心病慢性心衰患者和15例健康人1H-NMR的血浆代谢物谱,寻找与疾病和证候相关的标志性代谢物群,将其与代谢通路结合,为慢性心衰及证候的生物学基础研究提供新的方法和思路。
研究结果
(一)临床横断面流行病学研究结果
1.630例慢性心力衰竭患者以男性居多,构成比为58.25%。55岁以下患者占14.92%,55岁到70岁之间患者占35.24%,70岁以上患者占49.84%。纳入患者的原发病为冠心病、高心病和扩心病,其中冠心病患者占61.95%,高心病患者占29.22%,扩心病患者占8.83%。心功能I级患者占2.22%,心功能Ⅱ级患者人数占24.92%,心功能Ⅲ级患者占51.11%,心功能Ⅳ级患者占21.75%。合并症按出现频次高低依次为高血压,心律失常,糖尿病,脑血管意外,高血脂症等。
2.630例慢性心衰患者出现8种证候,其中气虚证为基本证候,其次为血瘀证和水停证,再次为阴虚证、痰浊证、阳虚证、热证和气滞证。证候组合方式有单一证型、证组合、三证组合、四证组合、五证组合和六证组合型。气虚证为最常见的单证型,占45.16%；二证组合以气虚血瘀最多,占53.98%；三证组合以气虚血瘀水停最多,占35.22%；四证组合以气虚血瘀阳虚水停最多,占23.9]%；五证组合以气虚血瘀阳虚水停兼夹痰浊证最多,占58.70%；六证组合仅1例,为气虚血瘀阳虚水停兼夹阴虚痰浊证。其中以三证组合方式为最常见,其次是四证组合和两证组合。性别、年龄、原发病因、心功能和并发症等可影响慢性心衰证候分布。
(二)慢性心衰证候生物学诊断模式研究
1.经T检验、ROC曲线分析和Logistic回归筛选出的气虚证指标为BASO、RBCHGB等；经T检验、ROC曲线分析和Logistic回归筛选出的血瘀证指标为：LYMPH、LYMPHL、MONO等；经T检验、ROC曲线分析和Logistic回归筛选出的痰浊证指标为：WBC、NEUT、LYMPH等；经T检验、ROC曲线分析和Logistic回归筛选出的水停证指标为：WBC、BASO、NEUT1等；经T检验、ROC曲线分析和Logistic回归筛选出的阴虚证指标为：WBC、MONO、EO等；经T检验、ROC曲线分析和Logistic回归筛选出的阳虚证指标为：RBC、HGB、MCH等。
2.运用神经网络MLP(多层感知器)方法对慢性心衰各证候的理化指标群进行建模处理,血瘀证测试样本和预测样本中的准确率分别为75.4%和82.4%；痰浊证测试样本和预测样本中的准确率分别为79.3%和83.3%；水停证测试样本和预测样本中的准确率分别为81.8%和81.0%；阴虚证测试样本和预测样本中的准确率分别为83.0%和82.4%；阳虚证测试样本和预测样本中的准确率分别为91.1%和90.5%。
(三)慢性心衰患者血浆代谢组学研究
1.应用主成分分析和正交偏最小二乘两种模式识别方法对慢性心衰患者和健康人血浆1H-NMR代谢组进行了判别分析,结果显示慢性心衰患者与健康对照组图中主成分积分值基本集中分布于椭圆形散点图(95%置信区内)的4个区域,无明显交叉和重叠,表明慢性心衰患者与健康人之间存在血浆成分代谢产物谱的显著差异。其中慢性心衰患者组乳酸、肌酸、脯氨酸等含量明显高于健康对照组,而组氨酸、甘氨酸、谷氨酸等含量低于健康对照组。
2.慢性心衰血瘀证患者与非血瘀证患者CPMG谱图差异代谢物包括组氨酸、甘氨酸、缬氨酸等下降,乳酸、丙氨酸、丙酮酸等升高；LED图谱差异代谢物主要为高密度脂蛋白下降、低密度脂蛋白和极低密度脂蛋白的升高。
3.慢性心衰痰浊证患者血浆CPMG图谱差异代谢物包括丙氨酸、葡萄糖、胆碱等下降,乳酸升高。血浆LED图谱差异代谢物包括高密度脂蛋白、低密度脂蛋白、极低密度脂蛋白和不饱和脂肪酸下降。
4.慢性心衰水停证患者血浆CPMG图谱差异代谢物包括葡萄糖、胆碱、TMAO等下降,乳酸、丙氨酸、乙酸等升高。血浆LED图谱差异代谢物包括低密度脂蛋白、极低密度脂蛋白和不饱和脂肪酸下降。
5.慢性心衰阴虚证患者血浆CPMG图谱差异代谢物包括葡萄糖、缬氨酸、脯氨酸等降低,乳酸、糖蛋白升高。血浆LED图谱差异代谢物为低密度脂蛋白、极低密度脂蛋白和糖蛋白的升高。
6.慢性心衰阳虚证患者血浆CPMG图谱差异代谢物包括葡萄糖、脂蛋白降低,乳酸、丙氨酸、谷氨酸、丙酮酸升高。血浆LED图谱差异代谢物包括谷氨酸、糖蛋白升高和高密度脂蛋白、低密度脂蛋白和极低密度脂蛋白的降低。
结论
1.通过研究,认识到慢性心衰发病以老年人为主的特点及病因分布情况,结合指南精神,提醒我们全方位、多靶点介入以控制危险因素并积极治疗高危人群原发病,有助于预防发展为心力衰竭,或延缓慢性心力衰竭发病进程。慢性心衰证候分布以气虚、水停、血瘀、痰浊、阴虚和阳虚为常见证候,气虚血瘀水停为关键病机,探讨慢性心衰的中医证型与心功能分级、中医药如何防治心力衰竭,减轻并发症,降低患者再住院率和死亡率有重要意义。
2.贫血倾向和肾功能损害是慢性心衰气虚证可能的生物学基础；红细胞体积改变,血液流变学改变,单核-巨噬细胞介导的炎症反应等为血瘀证可能的生物学基础；血脂紊乱,炎性反应、高尿酸水平等为痰浊证可能的生物学基础；炎性反应,高尿酸,补体系统抑制等可能为水停证的内在生物学基础；炎性反应,贫血倾向,血脂紊乱等为阴虚证可能的生物学基础；贫血倾向,肝功下降,免疫激活等为阳虚证可能的内在生物学机制。本研究在运用ROC曲线和逻辑回归分析后得到的理化指标相互印证和补充并阐述其生物学意义后,对慢性心衰主要证候相关理化指标群进行人工网络建模处理,在测试和预测样本中都得到较高准确率,因此在证候的生物学基础研究过程中应将多种数据发掘方法互参以揭示证候本质所在。
3.运用代谢组学方法对慢性心衰患者和健康人血浆分析结果显示OPLSDA模式识别效果优于PCA,可以降低临床样本不均一性,提高模式识别的分类效果,在临床数据分析中值得推广。慢性心衰与能量代谢、氨基酸代谢,糖代谢和脂代谢紊乱关系密切,反映慢性心衰状态下能量代谢紊乱、神经内分泌失调、免疫功能减弱、血液微循环障碍及抗损伤修复减退的病理机制。此外,慢性心衰各证候具有不同的代谢模式,所建模型能够将各组区分,其中小分子代谢物较大分子代谢物差异更明显,表明代谢组学技术及方法可通过代谢模式实现中医证型区分,为更好地将代谢组学方法用于疾病／证候的判别分析做了有益的探索。
Object ives
The purpose of the study of patients with chronic heart failure was to investigate the complicated TCM syndromes, in which the biological indexes used to build the diagnostic pattern for each syndrome based on data mining methods were adopted. We further analyzed the metabolites closely related to chronic heart failure and different syndromes by1H-NMR techniques, so as to provide new ideas in syndrome diagnosis, prevention and treatment of heart failure with TCM formulas.
Methods
1.Clinical cross-sectional study:630patients were enrolled and we discriminated syndromes under the criteria based on the demographic data, illness history as well as TCM four diagnostic information collected. Complicated TCM syndromes and related factors were described.
2.Biological diagnostic pattern study:100patients with CHF were included and their physical and chemical indexes were analyzed by T-test, ROC curve and logistic regression to build the diagnosis pattern by means of artificial networks.
3.The metabolic biomarker study:Plasma samples of46patients with chronic heart failure caused by coronary heart diseases and15healthy people were experimented by1H-NMR to find the metabolites related to chronic heart failure and different syndromes, PCA and OPLSDA methods were used and the results were compared.
Results
1.The male patients accounted for58.25%in630patients with CHF. Patients above70years occupied49.84%.Coronary heart diseases is the leading cause of chronic heart failure. Patients with NYHA cardiac function of grade III took up51.11%.The most common complications are hypertension, arrhythmia, diabetes diseases, cerebral vascular accident, hyperlipemia etc. There were8kinds of syndromes, qi deficiency was the most, followed by blood stasis and water retention, phlegm turbid, yin deficiency, yang deficiency, qi stagnation, heat. There were single syndrome to six syndrome combinations. Qi deficiency was the most common syndrome in single type, accounting for45.16%. Qi deficiency combined with blood stasis was the top two syndrome combination, accounting for53.98%. Qi deficiency and blood stasis combined with water retention was the top three syndrome combination, accounting for35.22%. Qi deficiency and blood stasis and water retention combined with Yang Deficiency syndrome was the top four syndrome combination, accounting for29.31%. Qi deficiency and blood stasis and water retention combined with yang deficiency as well as phlegm turbid was top five syndrome combination, accounting for58.70%. Three syndromes combination was the most common type. Sex, age, cause of illness, heart function and complications were related to the development of CHF.
2. Characteristic indexes of qi deficiency includes:BASO、RBC、HGB etc; Characteristic indexes of blood stasis includes:LYMPH、LYMPHL、MONO etc; Characteristic indexes of phlegm turbid includes:WBC、NEUT、LYMPH etc; Characteristic indexes of water retention includes:WBC、BASO、NEUT1etc; Characteristic indexes of yin deficiency includes:WBC、 MONO、EO etc; Characteristic indexes of yang deficiency includes:RBC、HGB、MCH etc. The accuracy of diagnosis pattern used by MLP was higher than80%on average for each syndrome in both training samples and validation samples.
3.PC A and OPLSDA methods were used to analyze the distinguished metabolites between the patients and healthy people, including Lac, Cr, Tyr etc, and the OPLSDA methods had better classification. The characteristic metabolites of the blood stasis syndrome were as follows: Lac, Ala His etc increased while Gly,Val, Glu etc reduced; The characteristic metabolites of the phlegm turbid syndrome were as follows:Lac increased while Ala, Glu, Cho, Pro, Gly, HLDL, VLDL\LDL, UFA reduced; The characteristic metabolites of the water retention syndrome were as follows:Lac, Ala, N-Ac, O-Ac increased while Glu, Cho, TMAO, Pro, VLDL\LDL, UFA reduced; The characteristic metabolites of the yin deficiency syndrome were as follows:Lac, N-Ac, O-Ac, VLDL\LDL increased while Glu, Val, Pro, Ala, Carnitine reduced; The characteristic metabolites of the yang deficiency syndrome were as follows:Lac, Ala, N-Ac, Glutamate increased while Glu, HLDL, VLDL\LDL reduced.
Conelusion
1.More attention should be paid to the old in prevention and treatment of CHF. Getting rid of the risk factors, controlling the complications and avoiding bad habits play an important role in reducing the mortality and re-hospitalization rate of chronic heart failure patients. Qi deficiency, water retention, blood stasis, phlegm turbid, yin deficiency and yang deficiency are the basic syndromes in this disease. Qi deficiency and blood stasis combined with water retention is the key pathogenesis, which can help clinical doctors get a better understanding of the syndrome differentiation in the treatment of CHF.
2.Qi deficiency syndrome related to anemia and decreased renal function; Blood stasis syndrome related to blood cell volume changes, inflammatory response etc; Phlegm turbid syndrome related to lipids disorder, inflammatory response, high UA level etc; Water retention syndrome related to inflammatory response, high UA level, immune activation etc. Yin deficiency syndrome related to inflammatory response, anemia, lipids disorder etc. Yang deficiency syndrome related to anemia, reduced liver function, immune activation etc. As far as the diagnosis model for each syndrome being concerned. We should make full use of all kinds of data mining methods to do the TCM syndrome research.
3.The OPLSDA methods have great potential to distinguish the metabolic biomarkers, better than PCA in this study, which should be widely applied in clinical studies. We figured out the metabolic patterns of patients with CHF, related to the glucose, protein, lipid metabolism as well as energy supplication, which reflect the patho-physiological mechanisms of the diseases, such as nerve-endocrine disorders, immune dysfunction, microcirculation disorder and so on. Different metabolites were found in each TCM syndrome of CHF, which could be obviously seen from the small molecular metabolites, provided new ideas of syndrome diagnosis as well as the prevention and treatment of chronic heart failure by Traditional Chinese Medicine.
研究目的
探讨慢性心衰证候分布组合特点及影响因素,对慢性心衰患者进行多项生物学指标检测和代谢组学核磁波谱分析,将一般统计学方法与数据挖掘方法相结合,在宏观和微观层面挖掘与疾病及证候相关的代谢物,并与代谢路径结合,提取敏感性和特异性强的证候特征指标群,为慢性心衰证候客观化诊断及中药复方干预提供参考依据。研究方法
1.临床横断面研究：全面采集630例慢性心衰患者人口学资料、现病史信息、中医四诊信息及诊断结果,对证候属性进行判别,描述慢性心衰证候分布特点和组合规律并对影响因素进行Logistic回归分析。
2.慢性心衰证候生物学诊断模式研究：检测符合纳入标准的100例慢性心衰患者临床生化指标及超声心动图结果,运用数据挖掘方法对各证候生物学指标进行相关分析和特征提取,在此基础上用神经感知器方法构建各证候生物学诊断模式。
3.慢性心衰患者血浆代谢组学研究：对比46例冠心病慢性心衰患者和15例健康人1H-NMR的血浆代谢物谱,寻找与疾病和证候相关的标志性代谢物群,将其与代谢通路结合,为慢性心衰及证候的生物学基础研究提供新的方法和思路。
研究结果
(一)临床横断面流行病学研究结果
1.630例慢性心力衰竭患者以男性居多,构成比为58.25%。55岁以下患者占14.92%,55岁到70岁之间患者占35.24%,70岁以上患者占49.84%。纳入患者的原发病为冠心病、高心病和扩心病,其中冠心病患者占61.95%,高心病患者占29.22%,扩心病患者占8.83%。心功能I级患者占2.22%,心功能Ⅱ级患者人数占24.92%,心功能Ⅲ级患者占51.11%,心功能Ⅳ级患者占21.75%。合并症按出现频次高低依次为高血压,心律失常,糖尿病,脑血管意外,高血脂症等。
2.630例慢性心衰患者出现8种证候,其中气虚证为基本证候,其次为血瘀证和水停证,再次为阴虚证、痰浊证、阳虚证、热证和气滞证。证候组合方式有单一证型、证组合、三证组合、四证组合、五证组合和六证组合型。气虚证为最常见的单证型,占45.16%；二证组合以气虚血瘀最多,占53.98%；三证组合以气虚血瘀水停最多,占35.22%；四证组合以气虚血瘀阳虚水停最多,占23.9]%；五证组合以气虚血瘀阳虚水停兼夹痰浊证最多,占58.70%；六证组合仅1例,为气虚血瘀阳虚水停兼夹阴虚痰浊证。其中以三证组合方式为最常见,其次是四证组合和两证组合。性别、年龄、原发病因、心功能和并发症等可影响慢性心衰证候分布。
(二)慢性心衰证候生物学诊断模式研究
1.经T检验、ROC曲线分析和Logistic回归筛选出的气虚证指标为BASO、RBCHGB等；经T检验、ROC曲线分析和Logistic回归筛选出的血瘀证指标为：LYMPH、LYMPHL、MONO等；经T检验、ROC曲线分析和Logistic回归筛选出的痰浊证指标为：WBC、NEUT、LYMPH等；经T检验、ROC曲线分析和Logistic回归筛选出的水停证指标为：WBC、BASO、NEUT1等；经T检验、ROC曲线分析和Logistic回归筛选出的阴虚证指标为：WBC、MONO、EO等；经T检验、ROC曲线分析和Logistic回归筛选出的阳虚证指标为：RBC、HGB、MCH等。
2.运用神经网络MLP(多层感知器)方法对慢性心衰各证候的理化指标群进行建模处理,血瘀证测试样本和预测样本中的准确率分别为75.4%和82.4%；痰浊证测试样本和预测样本中的准确率分别为79.3%和83.3%；水停证测试样本和预测样本中的准确率分别为81.8%和81.0%；阴虚证测试样本和预测样本中的准确率分别为83.0%和82.4%；阳虚证测试样本和预测样本中的准确率分别为91.1%和90.5%。
(三)慢性心衰患者血浆代谢组学研究
1.应用主成分分析和正交偏最小二乘两种模式识别方法对慢性心衰患者和健康人血浆1H-NMR代谢组进行了判别分析,结果显示慢性心衰患者与健康对照组图中主成分积分值基本集中分布于椭圆形散点图(95%置信区内)的4个区域,无明显交叉和重叠,表明慢性心衰患者与健康人之间存在血浆成分代谢产物谱的显著差异。其中慢性心衰患者组乳酸、肌酸、脯氨酸等含量明显高于健康对照组,而组氨酸、甘氨酸、谷氨酸等含量低于健康对照组。
2.慢性心衰血瘀证患者与非血瘀证患者CPMG谱图差异代谢物包括组氨酸、甘氨酸、缬氨酸等下降,乳酸、丙氨酸、丙酮酸等升高；LED图谱差异代谢物主要为高密度脂蛋白下降、低密度脂蛋白和极低密度脂蛋白的升高。
3.慢性心衰痰浊证患者血浆CPMG图谱差异代谢物包括丙氨酸、葡萄糖、胆碱等下降,乳酸升高。血浆LED图谱差异代谢物包括高密度脂蛋白、低密度脂蛋白、极低密度脂蛋白和不饱和脂肪酸下降。
4.慢性心衰水停证患者血浆CPMG图谱差异代谢物包括葡萄糖、胆碱、TMAO等下降,乳酸、丙氨酸、乙酸等升高。血浆LED图谱差异代谢物包括低密度脂蛋白、极低密度脂蛋白和不饱和脂肪酸下降。
5.慢性心衰阴虚证患者血浆CPMG图谱差异代谢物包括葡萄糖、缬氨酸、脯氨酸等降低,乳酸、糖蛋白升高。血浆LED图谱差异代谢物为低密度脂蛋白、极低密度脂蛋白和糖蛋白的升高。
6.慢性心衰阳虚证患者血浆CPMG图谱差异代谢物包括葡萄糖、脂蛋白降低,乳酸、丙氨酸、谷氨酸、丙酮酸升高。血浆LED图谱差异代谢物包括谷氨酸、糖蛋白升高和高密度脂蛋白、低密度脂蛋白和极低密度脂蛋白的降低。
结论
1.通过研究,认识到慢性心衰发病以老年人为主的特点及病因分布情况,结合指南精神,提醒我们全方位、多靶点介入以控制危险因素并积极治疗高危人群原发病,有助于预防发展为心力衰竭,或延缓慢性心力衰竭发病进程。慢性心衰证候分布以气虚、水停、血瘀、痰浊、阴虚和阳虚为常见证候,气虚血瘀水停为关键病机,探讨慢性心衰的中医证型与心功能分级、中医药如何防治心力衰竭,减轻并发症,降低患者再住院率和死亡率有重要意义。
2.贫血倾向和肾功能损害是慢性心衰气虚证可能的生物学基础；红细胞体积改变,血液流变学改变,单核-巨噬细胞介导的炎症反应等为血瘀证可能的生物学基础；血脂紊乱,炎性反应、高尿酸水平等为痰浊证可能的生物学基础；炎性反应,高尿酸,补体系统抑制等可能为水停证的内在生物学基础；炎性反应,贫血倾向,血脂紊乱等为阴虚证可能的生物学基础；贫血倾向,肝功下降,免疫激活等为阳虚证可能的内在生物学机制。本研究在运用ROC曲线和逻辑回归分析后得到的理化指标相互印证和补充并阐述其生物学意义后,对慢性心衰主要证候相关理化指标群进行人工网络建模处理,在测试和预测样本中都得到较高准确率,因此在证候的生物学基础研究过程中应将多种数据发掘方法互参以揭示证候本质所在。
3.运用代谢组学方法对慢性心衰患者和健康人血浆分析结果显示OPLSDA模式识别效果优于PCA,可以降低临床样本不均一性,提高模式识别的分类效果,在临床数据分析中值得推广。慢性心衰与能量代谢、氨基酸代谢,糖代谢和脂代谢紊乱关系密切,反映慢性心衰状态下能量代谢紊乱、神经内分泌失调、免疫功能减弱、血液微循环障碍及抗损伤修复减退的病理机制。此外,慢性心衰各证候具有不同的代谢模式,所建模型能够将各组区分,其中小分子代谢物较大分子代谢物差异更明显,表明代谢组学技术及方法可通过代谢模式实现中医证型区分,为更好地将代谢组学方法用于疾病／证候的判别分析做了有益的探索。
Object ives
The purpose of the study of patients with chronic heart failure was to investigate the complicated TCM syndromes, in which the biological indexes used to build the diagnostic pattern for each syndrome based on data mining methods were adopted. We further analyzed the metabolites closely related to chronic heart failure and different syndromes by1H-NMR techniques, so as to provide new ideas in syndrome diagnosis, prevention and treatment of heart failure with TCM formulas.
Methods
1.Clinical cross-sectional study:630patients were enrolled and we discriminated syndromes under the criteria based on the demographic data, illness history as well as TCM four diagnostic information collected. Complicated TCM syndromes and related factors were described.
2.Biological diagnostic pattern study:100patients with CHF were included and their physical and chemical indexes were analyzed by T-test, ROC curve and logistic regression to build the diagnosis pattern by means of artificial networks.
3.The metabolic biomarker study:Plasma samples of46patients with chronic heart failure caused by coronary heart diseases and15healthy people were experimented by1H-NMR to find the metabolites related to chronic heart failure and different syndromes, PCA and OPLSDA methods were used and the results were compared.
Results
1.The male patients accounted for58.25%in630patients with CHF. Patients above70years occupied49.84%.Coronary heart diseases is the leading cause of chronic heart failure. Patients with NYHA cardiac function of grade III took up51.11%.The most common complications are hypertension, arrhythmia, diabetes diseases, cerebral vascular accident, hyperlipemia etc. There were8kinds of syndromes, qi deficiency was the most, followed by blood stasis and water retention, phlegm turbid, yin deficiency, yang deficiency, qi stagnation, heat. There were single syndrome to six syndrome combinations. Qi deficiency was the most common syndrome in single type, accounting for45.16%. Qi deficiency combined with blood stasis was the top two syndrome combination, accounting for53.98%. Qi deficiency and blood stasis combined with water retention was the top three syndrome combination, accounting for35.22%. Qi deficiency and blood stasis and water retention combined with Yang Deficiency syndrome was the top four syndrome combination, accounting for29.31%. Qi deficiency and blood stasis and water retention combined with yang deficiency as well as phlegm turbid was top five syndrome combination, accounting for58.70%. Three syndromes combination was the most common type. Sex, age, cause of illness, heart function and complications were related to the development of CHF.
2. Characteristic indexes of qi deficiency includes:BASO、RBC、HGB etc; Characteristic indexes of blood stasis includes:LYMPH、LYMPHL、MONO etc; Characteristic indexes of phlegm turbid includes:WBC、NEUT、LYMPH etc; Characteristic indexes of water retention includes:WBC、BASO、NEUT1etc; Characteristic indexes of yin deficiency includes:WBC、 MONO、EO etc; Characteristic indexes of yang deficiency includes:RBC、HGB、MCH etc. The accuracy of diagnosis pattern used by MLP was higher than80%on average for each syndrome in both training samples and validation samples.
3.PC A and OPLSDA methods were used to analyze the distinguished metabolites between the patients and healthy people, including Lac, Cr, Tyr etc, and the OPLSDA methods had better classification. The characteristic metabolites of the blood stasis syndrome were as follows: Lac, Ala His etc increased while Gly,Val, Glu etc reduced; The characteristic metabolites of the phlegm turbid syndrome were as follows:Lac increased while Ala, Glu, Cho, Pro, Gly, HLDL, VLDL\LDL, UFA reduced; The characteristic metabolites of the water retention syndrome were as follows:Lac, Ala, N-Ac, O-Ac increased while Glu, Cho, TMAO, Pro, VLDL\LDL, UFA reduced; The characteristic metabolites of the yin deficiency syndrome were as follows:Lac, N-Ac, O-Ac, VLDL\LDL increased while Glu, Val, Pro, Ala, Carnitine reduced; The characteristic metabolites of the yang deficiency syndrome were as follows:Lac, Ala, N-Ac, Glutamate increased while Glu, HLDL, VLDL\LDL reduced.
Conelusion
1.More attention should be paid to the old in prevention and treatment of CHF. Getting rid of the risk factors, controlling the complications and avoiding bad habits play an important role in reducing the mortality and re-hospitalization rate of chronic heart failure patients. Qi deficiency, water retention, blood stasis, phlegm turbid, yin deficiency and yang deficiency are the basic syndromes in this disease. Qi deficiency and blood stasis combined with water retention is the key pathogenesis, which can help clinical doctors get a better understanding of the syndrome differentiation in the treatment of CHF.
2.Qi deficiency syndrome related to anemia and decreased renal function; Blood stasis syndrome related to blood cell volume changes, inflammatory response etc; Phlegm turbid syndrome related to lipids disorder, inflammatory response, high UA level etc; Water retention syndrome related to inflammatory response, high UA level, immune activation etc. Yin deficiency syndrome related to inflammatory response, anemia, lipids disorder etc. Yang deficiency syndrome related to anemia, reduced liver function, immune activation etc. As far as the diagnosis model for each syndrome being concerned. We should make full use of all kinds of data mining methods to do the TCM syndrome research.
3.The OPLSDA methods have great potential to distinguish the metabolic biomarkers, better than PCA in this study, which should be widely applied in clinical studies. We figured out the metabolic patterns of patients with CHF, related to the glucose, protein, lipid metabolism as well as energy supplication, which reflect the patho-physiological mechanisms of the diseases, such as nerve-endocrine disorders, immune dysfunction, microcirculation disorder and so on. Different metabolites were found in each TCM syndrome of CHF, which could be obviously seen from the small molecular metabolites, provided new ideas of syndrome diagnosis as well as the prevention and treatment of chronic heart failure by Traditional Chinese Medicine.
引文
[1]Greenberg B.J Treatment of heart failure:state of the art and prospectives[J]. Cardiovasc Pharmacol,2001,38:S59-S63.
[2]X.Guo etal.Prevention of remodeling in congestive heart failure due to myocardial infarction by blockade of the rennin-angiotensin system[J]. Cardiovasc. Ther,2005,3:717-732.
[3]Y.S.Oh,A.Y.Jong and D.T.Kim etal. Spatial distribution of nerve sprouting after myocardial infarction in mice[J].Heart Rhythm,2006,3:728-736.
[4]Thomas P.Cappola MD,ScM Molecular Remodeling in Human Heart Failure[J]. Journal of the American College of Cardiology.2008,2(15):137-138.
[5]Packer M. How should physicians view heart failure? The philosophical and physiological evolution of three conceptual models of the disease[J]. Am J Cardiol,1993,71:3C-11C.
[6]Pepper G,Lee RW. Sympathetic activation in heart failure and its treatment withβ-blockade[J]. Arch Intern Med,1999,159:225-234.
[7]Collucci WS. Molecular and cellular mechanisms of myocardial failure[J]. Am J Cardiol, 1997,80:15L-25L.
[8]Sabbath H,Shrove VG.Apoptosis in heart failure Prog[J].Cardiovasc Dis,1998,40:549-562.
[9]V.J.Dzau,M.Packer,and L.S.Lilly etal.Hollenberg and G.H.Williams, Prostaglandins in severe congestive heart failure relation to activation of the renin-angiotensin system and hyponatremia[J].N Engl J,1984,310:347-352.
[10]D. L.Mann and M.R.Bristow etal.Mechanisms and models in heart failure:the biomechanical model and beyond[J].Circulation,2005,111:2837-2849.
[11]M.R.Bristow,E.M.Gilbert and W.T.Abraham etal.Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure[J].Circulation,1996,94:2807-2816.
[12]G.MERIT-HF Study, Effect of metoprolol CR/XL in chronic heart failure:Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure(MERIT-HF) [J].1999,353:2001-2007.
[13]R.Sethi et al.Dependence of changes in beta-adrenoceptor signal transduction on type and stage of cardiac hypertrophy[J].Appl.Physiol,2007,102:978-984.
[14]P.A.Poole-Wilson et al.Rationale and design of the carvedilol or metoprolol European trial in patients with chronic heart failure[J]. Eur J Heart Fail,2002,4:321-329.
[15]D.F.Goldspink et al.Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo:the same or separate death pathways[J].Physiol.2004,89:407-416.
[16]M.Gallego etal.Spironolactone and captopril attenuates isoproterenol-induced cardiac remodelling in rats[J].Pharmacol Res,2001,44:311-315.
[17]M.S.Cuffe et al.Short-term intravenous milrinone for acute exacerbation of chronic heart failure:a randomized controlled trial[J].JAMA.2002,287:1541-1547.
[18]Small KM, Wagoner LE, and Levin AM, et al. Synergistic polymorphisms of betal-and alpha 2C-adrenergic receptors and the risk of congestive heart failure[J].N Engl J Med.2002,347:1135-1142.
[19]Paull JR, Widdop RE et al. Persistent cardiovascular effects of chronic rennin-angiotensin system inhibition following withdrawal in adult spontaneously hypertensive rats[J].J Hypertens 2001,19:1393-1402.
[20]S Oparil et al.Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension:a randomised,double-blind trial[J].Lancet,2007,370:221-229.
[21]Y.J.Xu et al.Mechanism of the positive inotropic effect of lysophosphatidic acid in rat heart[J]. Cardiovasc Pharmacol Ther,2002,7:109-115.
[22]B.Pitt et al.The effect of spirono lactone on morbidity and mortality in patients with severe heartfailure. Randomized Aldactone Evaluation Study Investigators[J].N Engl J Med,1999,341:709-717.
[23]B.Pitt et al.Eplerenone,a selective aldosterone blocker,in patients with left ventricular dysfunction after myocardial infarction[J].N Engl J Med,2003,348:1309-1321.
[24]翟淑波.充血性心力衰竭发病机制的研究进展[J].临床儿科杂志,2006,10(24)：851-853.
[25]Berkowitz R.B-type natriuretic peptide and the diagnosis of acute heart failure [J].Rev Cardiovasc Med,2004,5(4):3-16.
[26]Abasai Z, Karram T,Ellaham S,et al. Implications of the natriuretic peptide system in the pathogenesis of heart failure:diagnosis and therapeutic importance [J].Pharmacol Ther,2004,102(3):223-241.
[27]Jaime LP, Franc isco JC, Carm en AT, etal.Accuracy of B-type natriuretic peptide levels in the diagnosis of left ventricular dysfunction and heart failure:A systematic review[J]. EurJHeart Fai,2006,8:390-399.
[28]Yoshimura M, YasueHogava H. PathoPhysiological significance and Clinical application of ANP and BNP in patients with heart failure[J]. Can J Physiol Pharmaeol,2001,79:730-735.
[29]Ishi Junich, Rinsho B.Clinical utility of NT-proBNP, a new biomarker of cardiac function and heart failure [J]. J ClinPatho,2008,56(4):316-321.
[30]Michele E, Claudio P, Concetta P, et a.l Comparison of Brain Natriuretic Peptide (BNP) and N-Terminal ProBNP for Early Diagnosis of Heart Failure[J].ClinChem,2007,53:1289-1297.
[31]Manowitz N R, Mayor G H, Klepper M J, etal. Hypothyroidism and thyroidsike syndrome in patients with moderate to severe congestive heart failure[J]. Am J Ther,1996, 3(1):797-801.
[32]Koglin J, Pehlivanlj S, Schwaiblmair M, etal. Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure [J].J Am CollCardiol,2001,38 (5):1934-1941.
[33]薛礼美,陈晓虎等.CHF的神经内分泌激素、细胞因子变化的研究进展[J].医学综述2004,10(3)：146-150.
[34]Han W, Chartier D, L i D, etal. Ionic remodeling of cardiac purkinje cells by congestive heart failure[J]. Circulation,2001,104 (17):2095-2100.
[35]Verkerk AO, Veldkamp MW, Baartscheer A, et al. Ionic mechanism of delayed after depolarizations in ventricular cells isolated from human end stage failing hearts[J]. Circulation,2001,104 (22):2728-2733.
[36]Watanbe T, YamakiM, Yamauchi S, et al. Regional prolongation of ARI and altered restitution properties cause ventricular arrhythmia in heart failure[J]. Am JPhysiol,2002,282 (1):H218.
[37]Dipla K,Mattiello JA,Margulies K,et al.The sarcop lasmic reticulum and Na+-Ca2+ exchanger both contribute to the Ca2+ transient of failing human ventricular myocytes[J].Circ Res,1999,84:435-444.
[38]M.Yano et al.FKBP12.6-mediated stabilization of calcium-release channel(ryanodine receptor)as a novel therapeutic strategy against heart failure[J].Circulation,2003;107:477-484.
[39]S.E.Lehnart et al.Novel targets for treating heart and muscle disease:stabilizing ryanodine receptors and preventing intracellular calcium leak[J].Curr Opin Pharmacol,2007,7:225-232.
[40]M.Asahi et al.Regulation of sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatase by phospholamban and sarcolipin:implication for cardiac hypertrophy and failure[J].Trends Cardiovasc Med,2003,13:152-157.
[41]A.Ghatak,M.J.Brar and A.Agarwal et al.Oxy free radical system in heart failure and therapeutic role of oral vitamin E[J].Int J Cardiol,1996,57:119-127.
[42]F.Giordano,Oxygen,oxidative stress,hypoxia,and heart failure[J].J Clin Invest,2005, 115:500-508.
[43]Ghosh MC, Wang X, eta 1.Regulation of caleineurinby oxida-five stress [J].Methods Enzymol,2003,366:289-304.
[44]M.Keith,A.Geranmayegan and M.J.Sole etal.Increased oxidative stress in patients with congestive heart failure[J].J Am Coll Cardiol,1998,31:1352-1356.
[45]F.Qin et al.Inhibition of NADPH oxidase reduces myocardial oxidative stress and apoptosis and improves cardiac function in heart failure after myocardial infarction,Free Radic[J].Biol Med,2007,43:271-281.
[46]Y.T.Sia et al.Beneficial effects of long-term use of the antioxidant probucol in heart failure in the rat[J].Circulation,2002,105:2549-2555.
[47]I.Dalle-Donne,D.Giustarini,and R.Colombo et al.Protein carbonylation in human diseases[J].Trends Mol Med,2003,9:169-176.
[48]Cristina Banfi and Maura Brioschi et al,Oxidized proteins in plasma of patients with heart failure:Role in endothelial damage[J]. European Journal of Heart Failure,2008,10(3):244-251.
[49]C.D.Rollo,J.Carlson and M.Sawada,Accelerated aging of giant transgenic mice is associated with elevated free radicals process[J].Can J Zool,1996;74:606-620.
[50]Stefan Neubauer.The Failing Heart-An Engine Out of Fuel[J].N Engl Jmed,2007,356:1140-51.
[51]V.Lionetti et al.Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure[J].Cardiovasc Res,2005;66:454-461.
[52]L.A.Nikolaidis et al.Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion[J].Circulation,2004,109:962-965.
[53]I.Thrainsdottir etal.Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure[J]. Diab Vasc Dis Res,2004,1:40-43.
[54]S.Schmidt-Schweda and C.Holubarsch,First clinical trial with etomoxir in patients with chronic congestive heart failure[C].Clin.Sci.(Lond.),2000,99:27-35.
[55]陈齐红,覃数.肿瘤坏死因子-α和充血性心力衰竭.心血管病学进展,2004,25(2)：89-91.
[56]M.Sun et al.Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state[J]. Circulation,2007,115:1398-1407.
[57]M.Sun et al.Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction[J].Circulation,2004,110:3221-3228.
[58]Feldm an AM, Com bes A and W agner D,etal.The role of tumor necrosis factor in the pathophysiology of heart failure[J].J Am CollCardiol,2000,35(3):537-544.
[59]Levine B, KaLman, Maver L et al. Elevated circulation levels of tumor necrosis factor in severe chronic hear failure[J].N Engl J Med,1990,323(4):236-241.
[60]邱飞,王礼深.肿瘤坏死因子-α与心力衰竭的研究进展[J].国外医学药学分册,2003,30(6)：326-330.
[61]Kadokami T, Frye C, Lemster B, et al. Anti-tumor necrosis factor-aAntibody limits heart failure in a transgenic model [J]. Circulation,2001,104 (10):1094-1097.
[62]B radham WS,Moe G,Wendt KA, et al. TNF-alpha and myocardialmatrix metallo proteinases in heart failure:relationship to LV remodeling[J]. Am J PhysiolHeart Circ Physiol, 2002,282(4):H1288-H1295.
[63]Li Y Y,Mctierman CF, Feldman AM. IL-1 beta alters the expression of the receptor tyrosine kinase generEphA3 in neonatal rat cardiomyocytes[J]. Cardiovasc Res,1999,42: 162-172.
[64]Shioi T,Matsumori A, Kihara Y, et al. Increased exp ression of interleukin-1βand monocyte chemotactic and activating factor/monocyte chemo attractant protein 1 in the hypertrophied and failing heart with pressure overload [J]. CircRes,1997,81 (5):664-671.
[65]Torre-Amione G, Kapadia S, Benedict C, et al.Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction; a report from the studies of left ventricular dysfunction(SOLVD). J Am Collcardiol,1996,27:1202-1206.
[66]刘传亮,刘向群.白细胞介素与左心室收缩功能关系探讨[J].山东医药,2002,42(23)：48-49.
[67]Givertz MM, Collueei WS. New targets for heart failure therapy:endothelin, inflammatory, cytokines. oxidative stress[J].Lancet.1998,352(Suppl I):134-138.
[68]HocherB, George I, Rebstock J, etal. Endothelin system2dependent cardiac remodeling in renovascular hypertension [J]. Hypertension,1999,33 (3):816-822.
[69]Mulder P,Boujedanini H, Richard V, etal. Selective endothelin A versum combined endothelin-A/endothelin-B receptor blockade in rat chronic heart failure[J]. Circulation,2000, 102 (5):491-493.
[70]Martin P,BoujedainiH, RichardV, et al. Effect of a highly selective endothelin-converting enzyme inhibitor on cardiac remodeling in rats after myocardial infarction[J].Cardiovasc Pharmacol,2000,36 (5 supp 11):S367-S370.
[71]Pechanova O,Bernatova I, Pelouch V, etal. L-NAME-induced protein remodeling and fibrosis in the rat heart [J]. Physiol Res,1999,48 (5):353-362.
[72]K.T.Weber et al.Angiotensin Ⅱ and extracellular matrix homeostasis[J].Biochem Cell Biol, 1999,31:395-403.
[73]F.G.Spinale,M.L.Coker and S.R.Krombach et al.,Matrix metalloproteinase inhibition during the development of congestive heartfailure:effects on left ventricular dimensions and function[J].Circ Res.1999;364-376.
[74]J T Peterson,H.Hallak and L Johnson etal.,Matrix metalloproteinase inhibition attenuates left ventricular remodeling and dysfunction in a rat model of progressive heart failure[J].Circulation,2001,103:2303-2309.
[75]Spninale FG, Coker ML, Heung LJ, etal. A matrix metalloproteinase induction/ activation system exists in the human left ventricular myocardium and is up regulated in heart failure[J].Circulation,2000,102:1944-1949.
[76]Massie BM, Shah NB. Evolving trends in the epidemiologic factors of heart failure: rational for preventive strategies and comprehensive disease management [J]. Am Heart J 1997,133:703-712.
[77]American Heart Association.2002 Heart and Stroke Statistical Updata[C].Dallas,TX American HeartAssociation,2002:19.
[78]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.全国世纪之交心力衰竭学术研讨会纪要[J].中华心血管病杂志,2002,30(1)：226.
[79]KannelWB, Ho K, Thom T. Changing epidemiological features of cardiac failure[J]. Br Heart J,1994,72 (supp 1):S3-S9.
[80]上海市心力衰竭调查协作组.上海市1980、1990、2000年心力衰竭住院患者流行病学及治疗状况调查.中华心血管病杂志,2002,30(1)：24-27.
[1]Gu DF, Huang GY, He J, Wu XG, Duan XF. Investigation of prevalence and distributing feature of chronic heart failure in Chinese adult population[J]. Zhonghua Xin Xue Guan Bing Za Zhi,2003; 31 (1):326.
[2]王娟,陈婵,张鹏等.口服中药治疗慢性心衰随机对照试验的系统评价[J].中华中医药杂志,2011,26(12)：2830-2840.
[3]吴红金,袁国会.心力衰竭中西医结合治疗学[M].北京：清华大学出版社,2008：6.
[4]谭璐芸.郭维琴治疗心力衰竭经验介绍[J].云南中医学院学报,2000,(23)2：43.
[5]赖旭峰,单赤军.邓铁涛教授从脾论治慢性充血性心力衰竭经验[J].河北中医,2001,12(23)12：909.
[6]周仲英等.益阴助阳活力血通脉法治疗充血性心力衰竭的临床研究[J].南京中医药大学学报,1998,12(3)：34.
[7]薛长玲.董燕平治疗慢性心力衰蝎经验[J].中医药学刊,2004,4(17)：2250.
[8]曹雪滨,胡元会,王士雯.充血性心力衰竭辨证分型与血管活性的关系[J].辽宁中医杂志,1999,26(10)：441-42.
[9]郑筱英.中药新药临床研究指导原则[M].中国医药科技出版社,2002,5(1)：79-80.
[10]朴勇洙,冯大鹏,蔡宏宇.充血性心力衰竭的中医概述[J].中华实用中西医杂志,2003,3(16)：479.
[11]陈可冀,廖家祯,肖镇祥.心脑血管疾病研究[M].上海：上海科学技术出版社,1998：28.
[12]黄永生.心衰论治.湖南中医药导报,2000,6(9)：3.
[13]杨培君,杨磊.充血性心力衰竭的中医证治概要[J].陕西中医学院学报,2003,25(1)2-5.
[14]腾国华,程君.心衰的病因病机及其辨证轮治[J].中医药学刊,2004,22(7)：1331.
[15]狄灵,梁君昭.心力衰竭辨证的临床思路与方法[J].中医杂志,2002,43(1)：67.
[16]黄平东,罗懿明,黄衍寿等.充血性心力衰竭中医证型特征及其演变规律的临床观察[J].中西医结合心脑血管病杂志,2003,1(12)：685-686.
[17]王振涛.充血性心力衰竭辩治体验[J].四川中医,2005,23(6)：9-10.
[18]屈营,张明谦.辨证治疗慢性心衰的临床体会[J].中医药学刊,2005,23(5)：951.
[19]张瑞华,焦增绵,马丽红.慢性充血性心力衰竭的中医辨证论治[J].中国医药学报,2002,17(7)：440-441.
[20]许心如.心力衰蝎的中医辨证施治[J].北京中医,1959,(3)：10.
[21]赵淳.慢性心力衰竭现代治疗进展及中医诊治思路探讨[J].中国中医急症2006.2(15)：158-163.
[22]缪灿铭.心力衰竭胆固醇水平与中医辨证候及病变关系的临床探讨[J].中医研究,2003,28(3)：28
[23]梁东辉.充血性心力衰竭的辨证分析及中西医结合治疗规律初探[J].实用中西医结合杂志,1997,10(11)：1069.
[24]贺泽龙,郭振球.充血性心力衰竭中医证候的临床回顾性调查研究[J].湖南中医学院学报,2003,23(5)：33-36.
[25]周英.心血管病表现心虚证患者左心舒张功能观察[J].中国中西医结合杂志,1995,15(1)：13-14.
[26]苗阳,赵文静,荆鲁,等.中西医结合治疗慢性心力衰竭的回顾性分析[J].中国中西医结合杂志,2008,28(5)：406-409.
[27]沈建平,王德春.充血性心力衰竭心虚证与心功能关系的探讨[J].辽宁中医杂志,1997,24(6)：245.
[28]蒋梅先,彭鹏,唐静芬等.心肾同病等病机与充血性心力衰竭循环激素的关系[J].上海中医药大学学报,2000,14(1)：27-29.
[29]周杰.高晓玲等.充血性心力衰竭患者心钠素与中医辨证分型相关性的临床研究[J].中 国中西医结合杂志,2003,3(16)：1322-1 324.
[30]曹雪滨,王士雯等.充血性心力衰竭中医辨证分型与心功能的关系[J].新中医,2000,32(2)：37-39.
[31]曹雪滨,胡元会等.充血性心力衰竭中医辨证分型与活性肽的关系[J].辽宁中医杂志,1999,26(10)：441-442.
[32]潘光明,邹旭,林晓忠等.心力衰竭患者脑钠肽与中医辨证分型相关性的临床研究[J].新中医,2006,38(4)：33-34.
[33]陈国通,陈永忠,邹襄,B型利钠肽与慢性心力衰竭中医证型的关系[J].中外医疗.2010,29(24)：53-54.
[34]邢晓博,刘福颂,张丙印.氨基末端B型脑钠肽前体、高敏C反应蛋白与脾肾阳虚型慢性心力衰竭的相关性探讨[J].中国医药导报,2011,8(32)：31-32.
[35]董其美,顾景淡,等.心脏病的中医虚证分型与左心功能关系的探讨[J].中西医结合杂志,1985,(5)：148-150.
[36]周杰,高晓玲,张宝州,等.充血性心力衰竭患者中医辩证分型与左心室功能不全的相关性研究[J].中医杂志.2003,44(8)：615-616.
[37]郑关毅,刘贵灿.心气虚患者左心室功能的多谱勒超声心动图[J].实用中西医结合杂志,1997,10(3)：1278.
[38]邓铁涛.中医诊断学[M].上海：上海科技出版社,1984.
[39]中国中西医结合研究会虚证与老年病专业委员会.中医虚证辨证参考标准[J].中西医结合杂志,1986,6(10)：598.
[40]中国中西医结合研究会活血化瘀专业委员会-血瘀证诊断标准[J].中西医结合杂志,1987,7(3)：129.
[41]蔡晓丽.慢性心力衰竭各证型与甲状腺激素水平的特征研究[D].广州中医药大学,2011：10-11.
[42]徐家新,钟志戎.充血性心力衰竭患者中医辨证与甲状腺激素变化的相关性研究[J].河北中医,2004；26(10)：732-733.
[43]缪灿铭,李雪山,林凯旋等.甲状腺激素水平与心力衰竭的功能分级及中医辨证的关系[J].光明中医,2003；18(105)：2-5.
[44]周杰,高晓玲.充血性心力衰竭中医辨证分型与心功能参数及甲状腺激素相关性的临床研究[J].中国中西医结合杂志,2004;,24(10)：872-874.
[45]薄艳丽.慢性心力衰竭阳虚证型与甲状腺激素关系的研究[D].广州：广州中医药大学,2009：48-54.
[46]张启华.充血性心力衰竭患者血清C即水平的变化及与心功能的关系[J].中外医疗,2008,17：37.
[47]陈瑞,廖远芬,梁凤霞等.充血性心力衰竭心气、阳虚证与肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-10的关系[J].中国中医药信息杂志,2003,10(8)：14-16.
[48]陈瑞,廖远芬,梁凤霞等.充血性心力衰竭心气(阳)虚证与肿瘤坏死因子-a、白细胞介素-6关系的探讨[J].湖北中医杂志,2003,25(5)：10-11.
[49]万智,宋刚.心力衰竭心肾阳虚／气阴两虚型与白细胞介素-6的关系研究[J].新疆中医药,25(3)：16-18.
[50]刘革命,熊尚全,马成富.慢性心力衰竭中医辨证分型与血浆NO及TNF-a含量的关系[J].山东中医杂志,2004,23(2)：71-72.
[51]商俊芳,周杰,高晓玲,等.充血性心力衰竭中医辨证分型与左心功能不全及心钠素、内皮素的相关性研究[J].中国中医药信息、杂志,2010,17(9)：23-36.
[52]郭跃进,郑春盛,詹萍.慢性心力衰竭血清sFas、外周血单个核细胞凋亡与心功能及中医证型的关系[J].福建中医学院学报,2005,15(6)：1-3.
[53]朱珍道,林求诚.心肾阳虚型充血性心力衰竭患者红细胞内ATP酶、SOD、钠钾钙镁及血清LPO的变化及其相互关系[J].实用中西医结合杂志,1998,11(2)：131-132.
[54]韩丽华,王振涛,牛晓亚等.充血性心衰阳虚证与免疫功能及血流变的关系[J].河南中医,1996,16(6)：344-346.
[55]殷鑫,王相东,刘晓燕.循证医学对四诊客观化研究的启示[J].中国中医基础医学杂志,2006,12(4)：299-300.
[56]邱德有,吴小红,黄璐琦.现代生命科学技术对中医药发展的影响[J].世界科学技术-中医药现代化,2001；3(2)：12-16.
[57]王永炎,张志斌.再议完善辨证方法体系的几个问题[J].天津中医药,2007,,24(1)：1-4.
[1]颜贤忠,赵剑字,彭双清,廖明阳.代谢组学在后基因时代的作用[J].波谱学杂志,2004,21(2)：263-270.
[2]许国旺,杨军.代谢组学及其研究进展[J].色谱,2003,21(4)：316-320.
[3]李晶,吴晓健,刘吕孝,元英进.代谢组学研究中数据处理方法的应用[J].药学学报,2006,41(1)：47-53.
[4]HORNING MG, MURAKAM IS, HORNING EC. Analyses of phospholipids,ceramides, and cerebros ides by gas chromatography and gas chromatography mass spectrometry[J]. Am J Clin Nutr,1971,24(9):1086-1096.
[5]NICHOLSON JK,LINDON JC,HOLMES E. Metabonomics:understanding the metabolic responses of living systems to patho-physiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenbiotica,1999,29(11):1181-1189.
[6]NICHOLSON JK,BOLLARD ME,LINDON JC, etal.Metabonomics:a platform for studying drug toxicity and gene function[J].Nat Rev Drug Discov,2002,1(2):153-162.
[7]BRINDLE JT,ANTT IH,HOLMES E,etal.Rapid and non invasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics[J]. NatMed, 2002,8(12):1439-1444.
[8]WATERS NJ,HOLMES E,WATERFIELD CJ,etal. NMR and pattern recognition studies on liver extracts and intact livers from rats treated with a-naphthy lisothiocyanate [J].BiochemPharmacol,2002,64(1):67-77.
[9]HOLMES E,ANTT IH. Chemo metric contributions to the evolution of metabonomics: mathematical solutions to characterizing and interpreting complex biological NMR spectra[J].Analyst,2002,127(12):1549-1557.
[10]FIEHN O. Metabolic networks of Cucurbita maxima phloem[J].Phytochemistry,2003, 62(6):875-886.
[11]朱航,唐惠儒,张许,刘买利.基于NMR的代谢组学研究[J].化学通报.2006,69(7)：1-9.
[12]HOLMES E,NICHOLSON JK,TRANTER G.Metabonomic characterization of genetic variations in toxicological and metabolic responses using probabilistic neural networks[J].ChemResToxicol,2001,14(2):182-191.
[13]KEUN HC,EBBELS TMD,ANTT IH, etal.Analytical reproducibility in 1H NMR-Based metabonomic urinalysis[J].ChemResToxicol,2002,15(11):1380-1386.
[14]LINDON JC,HOLMES E,NICHOLSON JK,Recent developments and applications of NMR-based metabonomics[J].Chin J MagnResonance,2006,23(1):101-127.
[15]赵剑宇,颜贤忠.基于核磁共振的代谢组学研究进展[J].国外医学药学分册.2004,31(5)：308-312.
[16]刘昌孝.代谢组学的发展于药物研究开发[J].天津药学.2005,17(2)：1-6.
[17]Nicholson JK, Wilson ID. High resolution proton magnetic resonance spectroscopy of biological fluids[J].Prog Nucl MagRes Spectrosc,1989,21(4):449. [18]TangH, WangY, Nicholson JK, etal. Use of relaxation-edited one-dimensional and two dimensional nuclear magnetic resonance spectroscopy to improve detection of small Metabolites in blood plasma[J].Anal Biochem,2004,325(3):260.
[19]Hall BM, Thompson NA, Nicholson JK, etal. A metabonomic investigation of heap to toxicity using diffusion-edited'HNMR spectroscopy of blood serum[J].Analyst,2003,128(7): 814.
[20]Gamache PH,Meyer DF,Granger MC,etal. Metabolomic applications of Electro chemistry/massspectrometry[J].J AmSocMassSpectrom,2004,15:1717.
[21]陈慧梅.代谢组学及其研究方法和应用[J].肾脏病与透析肾移植杂志,2005,14(1)：59-63.
[22]HOLMES E,N ICHOLLS AW,LINDON JC,etal.Chemo metric models for toxicity classification based on NMR spectra of biofluids[J].Chem ResToxicol,2000,13(6):471-478.
[23]ROBERTSON DG,RE ILYMD,SIGLER RE, etal.Metabonomics:evaluation of nuclear magnetic resonance(NMR) and pattern recognition technology for repid in vivo screening of liver and kidney toxicants[J].ToxicolSci,2000,57(2):326-337.
[24]LU G,WANG JS,ZHAO XJ,etal.Study on gender difference based on metabolites in urine by ultra high performance liquid chromatography/time of flight mass spectrometry[J].Chin J Chromatogr,2006,24(2):109-113.
[25]徐旻,林东海,刘昌孝.代谢组学研究现状与展望[J].药学学报,2005,40(9)：769-774.
[26]BECKONERT O, BOLLARD ME, EBBELS TMD, etal. NMR based metabonomic toxicity classification:hierarchical cluster analysis and K-nearest-neighhour approach [J]. Anal Chim Acta,2003,490(1-2):3-15.
[27]Nicholls AW, Nicholson JK, Haselden JN, etal. A metabonomic approach to the investigation of drug-induced phospholipidosis:an NMR spectroscopy and pattern recognition study [J], Biomarkers,2000,5(6):410-423.
[28]Griffin JL, Bollard ME. Metabonomics:Its potential as a tool in toxicology for safety assessment and data integration[J].Curr Drug Metab,2004,5:389-398.
[29]Nicholson JK, Connelly J, Lindon JC, et al. Metabonomics:a platform for studying drug toxicity and gene function[J].Nature,2002,1:153-161.
[30]Slim RM, Robertson DG., Albassam M, etal. Effect of dexamethasone on the metabonomics profile associated with phosphodiesterase inhibitor-induced vascular lesions in rats[J], Toxicol Appl Pharmacol,2002,183:108-116.
[31]Lehman Mckeeman LD, Car BD. Metabonomics:Application in predictive and mechanistic toxicology[J]. Toxicol Pathol,2004,32(Suppl.2):94-95.
[32]Azmi J, Griffin JL, Shore RF, et al. Chemometric analysis of biofluids following toxicant induced hepatotoxicity:A metabonomic approach to distinguish the effects of 1-naphthylisothiocyanate from its products[J]. Xenobiotica,2005,35(8):839-852.
[33]Warne MA, Lenz EM, Osborn D, et al. An NMR-based metabonomic investigation of the toxic effects of 3-trifluoromethyl-aniline on the earthworm Eisenia veneta[J]. Biomarkers,2000,5(1):56-72.
[34]Shockcor JP, Holmes E. Metabonomic applications in toxicity screening and disease diagnosis[J].CurrTopMed Chem,2002,2:35-51.
[35]Mar E Bollard, Elizabeth G. Stanley, John C. Lindon, Jeremy K. Nicholson, Elaine Holmes. NMR-based metabonomic approaches for evaluating physiological influences in biofluid composition[J]. NMR Biomed,2005,18:143-162.
[36]Brindle J T, Antti H, Homes E, Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H NMR based metabonomics[J]. Nat Med,2002, 8(12):1439-1444.
[37]Harald Mischak, Joshua J.Coon, Jan Novak, Eva M. Weissinger, Joost Schanstra,and Anna F. Dominiczak, Capillary electrophoresis-mass spectrometry as a powerful tool in biomarker discovery and clinical diagnosis:an update of recent developments[J].Mass Spectrom Rev.2009,28(5):703-724
[38]Zimmerli LU, Schiffer E, Zurbig P, Kellmann M, Mouls L, Pitt A, Coon JJ, Schmiederer RE, Mischak H, Peter K, Kolch W, Delles C, Dominiczak AF. Urinary proteomics biomarkers in coronary artery disease[J]. Mol Cell Proteomics,2008,7:290-298.
[39]Snell-Bergeon JK, Maahs DM, Ogden LG, Kinney G Hokanson JE, Schiffer E, Rewers M, Mischak H. Evaluation of urinary biomarkers for coronary artery disease, diabetes, and diabetic kidney disease[J]. Diabetes Technol Ther,2009; 11(1); 1-9.
[40]Martin JC, Canlet C, Delplanque B,etal.'HNMR metabonomics can differentiate the early atherogenic effect of dairy products in hyperlipidemichamsters[J], Atherosclerosis,2009,206:127-133.
[41]Yang J, Xu GW, Hong QF, et al. Discrimination of type 2 diabetic patients from healthy controls by using metabonomicsmethod based on their serum fatty acid profiles[J].JChromatogrB,2004,813:53-58.
[42]Hodavance MS, Ralston SL, Pelczer I. Beyond blood sugar:the potential of NMR-based metabonomics for type 2 human diabetes, and the horse as a possible model[J].Anal Bio anal Chem,2007,387:533-537.
[43]Whitehead TL, Emmons TK. Applying in vitro NMR spectroscopy and 1H NMR metabonomics to breast cancer characterization and detection[J],Prog Nucl Magn Reson Spectrosc,2005,47:165-174.
[44]Yang J, Xu GW, Zheng YF, et al. Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive result from hepatitis and hepatocirrhosis diseases[J].JChromatogrB,2004,813:59-65.
[45]Li F, Lu X, Liu H, etal.A pharmacometabonomic study on the therapeutic basis and metabolic effects of Epimediambrevicornum Maxim on hydrocortisone induced rat using UPLC-MS[J].BiomedChromatogr,2007,21 (4):397-405.
[46]王喜军,孙文军,孙晖,等.CC14诱导大鼠肝损伤模型的代谢组学及茵陈蒿汤的干预 作用研究[J].世界科学技术：中医药现代化,2006,8(6)：101-106.
[47]Kim HK, Choi YH, Erkelens C, etal.Metabolic fingerprinting of Ephedra species using 1H-NMR spectroscopy and principal component analysis[J].ChemPharmBull,2005,53(1):105-109.
[48]Susan J Murch, H P Vasantha Rupasinshe, D Goodenowe et al. A metabolomic analysis of medicinal diversity in Huangqin (Scutellaria baicalensis Georgi)genotypes:discovery of novel compounds[J].Plant Cell Repots,2004,23(6):419-425.
[49]齐炼文,李萍,赵静.代谢组学与中医药现代研究[J].世界科学技术-中医药现代化,2008,8(6)：79-86.
[50]樊夏雷,刘文英,王广基等.基于GC/TOF/MS的关木通肾毒性代谢组学研究[J].毒理学杂志,2007,21(4)：323.
[51]张杰,李浸.关于中医证候物质基础研究路径的思考[J].中国中医基础医学杂志,2007,13(5)：394-395.
[52]申维玺.论中医“证本质”的科学内涵[J].中国中医基础医学杂志,2001,7(6)：10-14.
[53]吴巧凤,颜贤忠,唐勇,等.代谢组学在我国中医药领域的应用[J].四川中医,2008,26(3)：7-9.
[54]董飞侠,黄迪,何立,贾伟.Ⅲ期慢性肾病肾阳虚证患者尿液代谢组学特征的研究.中华中医药杂志(原中国医药学报),2008,23(12)：1109-1113
[55]Wang Yong, Li Zhongfeng, Chen Jianxin etal. Study of mini-pig serum of coronary heart disease(chronic myocardial ischemia)with syndrome if blood stasis based on nuclear magnetic resonance metavolomics.Chinese Journal of Analytical Chemistry.2011(8),1274-1278.
[56]Li L,Wang JN,Ren JX,et al.Metabonomics analysis of the urine of rats with Qi deficiency and blood stasis syndrome based on NMR techniques中国科学通报(英文版),2007,52(22)：3068-3073.
[1]中华医学会心血管病学分会.慢性心力衰竭诊断治疗指南[J].中华心血管病杂志,2007,35(12)：1076-1095.
[2]中国中西医结合研究会活血化瘀研究委员会.血瘀证诊断标准[J].中西医结合杂志,1987,7(3)：129.
[3]沈自尹.中医虚证辨证参考标准[J].中西医结合杂志,1989,9(2)：11.
[4]朱文峰,王永炎.中医临床诊疗术语-证候部分[M].北京：中国标准出版社,1997：8-85.
[5]徐迪华,徐剑秋.中医量化诊断[M].南京：江苏科学技术出版社,1997：1-152.
[6]吴焕林,阮新民,罗文杰,等.319例冠心病患者证型分布聚类分析及证型诊断条件的确立[J].中国中西医结合杂志,2007,27(7)：616-617.
[7]欧爱华,罗翌,严夏,等.SARS与急性上呼吸道感染中医证候分型及指标数量化方法的探讨[J].中国卫生统计,2006,23(4)：309-311.
[8]Kannel WB, Ho K, Thom T. Changing epidemiological features of cardiac failure[J]. Br Heart J,1994,72 (supp 1):S3-S9.
[9]刘莹,陈庆伟,吴庆,等.老年人增龄、性别差异与冠心病的相关性研究[J].重庆医科大学学报,2010,35(3)：403-407.
[10]顾东风,黄广勇,何江,等.中国心力衰竭流行病学调查及其患病率[J].中华心血管病杂志,2003,31(1)：3-6.
[11]KalonKLH, JoanLP, WilliamBK, etal.The epidemiology of heart failure:TheFramingham Study[J].JAmCollCardiol,1993,22(4):6A-13A.
[12]中国心血管健康多中心合作研究组.中国心力衰竭流行病学调查及其患病[J]中华血管病杂志,2003,31(1)：3-6.
[13]谭璐芸.郭维琴治疗心力衰竭经验介绍[J].云南中医学院学报,2000,(23)2：43.
[14]曹雪滨,胡元会,王士雯.充血性心力衰竭辨证分型与血管活性的关系[J].辽宁中医杂志,1999,26(10)：441-42.
[15]陈婵.基于数据挖掘的冠心病心力衰竭中医证候因素及生物学基础研究[D].北京：北京中医药大学,2010：35-45.
[16]文川,程伟.206例冠心病心纹痛患者问诊资料与中医辨证关系的探讨[J].湖北中医杂志,2002,(10)：3
[17]王娟,陈婵,张鹏等.口服中药治疗慢性心衰随机对照试验的系统评价[J].中华中医药杂志,2011,26(12)：2830-2840.
[1]邱德有,吴小红,黄璐琦.现代生命科学技术对中医药发展的影响[J].世界科学技术-中医药现代化,2001；3(2)：12-16.
[2]Ezekowitz JA, M calister FA, Arm strong PW, etal.Anemia is common in heart failure and is associated with poor outcomes[J]. Circulation,2003,107:223-225.
[3]VanderMeer P, Voors AA, Lipsic E, etal Erythropoietin in cardio vascular diseases[J]. EurHeart,2004,25:285-291.
[4]SILVERBERG D S, WEXLER D, BLUM M, et al.The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe,resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations [J]. JAmCollCardiol,2000,35:1737-1744.
[5]TANNER H, MOSCH OVITI S G, KUSTER GM,et al. The prevalence of anemia in chronic hear t failure[J]. Int JCardiol,2002,86:115-121.
[6]MACDOUGALL I C. T he role of ACE inhibitors and angiotensin receptor blockers in the response to epoetin[J]. Nephr ol Dial Transplant,1999,14:1836-1841.
[7]CROMIE N, LEE C, STRUTH ERS AD. Anemia in chronic heart failure:What is its frequency in the UK and its underlying cause? [J]. Heart,2002,87:377-378.
[8]McalisterFA,Stewart S,Ferrua S,etal. Multi disciplinary strategies for the management of heart failure patients at high risk for admission:a systematic review of randomized trials[J].J Am Collcardiol,2004,44(4):810-819.
[9]曹雪滨,胡元会,王士雯.充血性心力衰竭辨证分型与血管活性的关系[J].辽宁中医杂志,1999,26(10)：441-42.
[10]Anand R, LatiniR, MassonS, etal.C-Reactive Protein in Heart Failure Value and the Effect of Valsartan[J]. Circulation,2005,112:1428-1434.
[11]Anand S, YenJ, FlreaVG, etal. Prognostic of neutron philandlymPhoeyteeounts in heart failure:results from Val-HeFT Program and abstracts from the American College of Cardiology 53rd AnnualSeientifieSession;Mareh7-10,2004;NewOrleansLouisiana. Abstract.1163-1211.
[12]张道杰.F-800血液分析仪对血瘀证的诊断价值[J].山东中医学院学报1995；19(5)：325-326
[13]刘正兴,王青.低T3综合症与充血性心力衰竭[J].疑难病杂志,2002,1(1)：54-65.
[14]CHEN PU, HE SH,WANG LH, et al. Relation between thyroxine and primary disease in congestive heart failure children [J].Chin J Emerg Med,2003,12:191-192.
[15]周杰,高晓玲,张宝州.充血性心力衰竭中医辨证分型与心功能参数及甲状腺激素相关性的临床研究[J].中国中西医结合杂志,2004,24(10),872-874.
[16]Horwich TB, Hamilton MA, MacLellan WR. et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure[J]. J Card Fail. 2002,8(4):216-224.
[17]ZOCCAL I C, MAIO R, MALLAMACI F. Uric acid and endothelial dysfunction in essential hypertension[J].Am Soc Nephrol,2006,17:1466-1471.
[18]SANCHEZ2LOZADA L G, NA KA GAWA T, KANG D H, etal. Hormonal and cytokine effect s of uric acid[J].Curr Opin Nephrol Hypertens,2006,15:30-33.
[19]L EYVA F, AN KER S, SWAN J W, etal. Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure [J]. Eur Heart J,1997,18:858-865.
[20]沈倩波,许顶立,高锦雄等.睡眠呼吸障碍对高血压患者血尿酸的影响[J].心肺血管病杂志,2006,25(3)：150-152.
[21]VIAZZI F, PARODI D, L EONCINI G, et al. Serum uric acid and target organ damage in primary hyper-tension[J].Hypertension,2005,45:991-996.
[22]FAN G J, ALDERMAN M H. Serum uric acid and cardiovascular mortality the N HANES I Epidemiologic follow-up study,1971-1992 [J]. JAMA,2000,283:2404-2410.
[23]RdkerPM, RifaiN, CiearfieldM, etal.Measurement of C-reactive protein for the targeting of stain therapy in the Primary Prevention of acute coronary events[J].NEnglJMed, 2001,82(1):256-267.
[24]LatinIR, AnandS, MaSSonS,etal. C-reactive protein in 4202 patients with moderate heart failure in Val-HeFT[J]. EurJHeartFail(Suppl),2004:3:112-114.
[25]SakataY, YamamotoK, ManoT, etal.Activation of matrix metal-proteinases-Proceeds left ventricular remodeling in hypertensive heart failure rats:its inhibition as a Prima-effect of angiotensin-everting enzyme inhibitor[J].Circulation,2004:109(17):21-43.
[26]Alons MarlinezJL, Liorente DiezB, Eehegara AgaraM, etal.C-reaetive proteinasa predictor of improvement alldre admission in heart failure[J].EurJHeartFail 2002,4:331-336.
[27]VanhouRePM.Endothelium dependent hyperpolarization beyond nitricoxide and eyelieGMP[J].Circulmion,1995:93(11):3337-3349.
[28]MattusehF,DufaUXB,HeineO,etal.Reduction of the plasma eoneentration of C-reactive protein following nine months of endurance training[J].IntJ SportsMed,2000:21(1):21-24.
[29]刘福明,赵志英,唐蜀华.甲状腺激素与充血性心力衰竭相关性研究进展[J].中国临床医学,2006,13(3)
[30]MadsenB, KellerN.ChristiansenE.Prognostie Value of plasma Eateeholamine Plasmaren activity, and plasma atrial natriuretic peptide at rest and during exercise in congestive heart failure:comparison with clinical evaluation, ejection fraction and exercise capacity[J].JCardFail,1995,1:207-216.
[31]AN KER SD,DOEHNER W,RAUCHHAUS M,etal.Uric acid and survival in chronic heart failure:validation and application in metabolic,functional, and hemodynamic staging[J].CirCUlation,2003,107:1991-1997.
[32]李彬,黄艳霞,廖玉华等.慢性心力衰竭患者血尿酸与细胞因子变化的相关性研究[J].实用医学杂志,2003,19(8)：858-859.
[33]CEN GEL A,TURKOGLU S,TURFAN M,etal.Serum uric acid levels as a predictor of in-hospital death in patients h0Spitalized for compensated heart failure[J].Acta Cardiol,2005,60:489-492.
[34]GROOTE P D,MOUQUET F,LAMBL IN N,etal.Serum uric acid is a powerful predictor of survival in paltient s with stable chronic heart failure receiving beta-blocker therapy[J].Circulation,2007,116:650-650.
[35]Muscari A,Bozzoli C,Puddu GM,et al.Association of serum C3 levels with the risk of myocardial infarction[J].Am J Med,1995;98(4):357-364
[36]Muscari A,Massarelli G,Bastagli L,et al.Relationship between serum C3 levels and traditional risk factors for myocardial infarction[J].Acta Crdrdiol,1998;53(6):345-354.
[37]Yudkin JS.Relationlship of serum C3 complement with insulin resistanceand coronary heart disease-cause,consequence or common antecedent?Eur Heart J 2000;21(13):1036-1039
[38]Muscari A,Massarelli G,Bastagli L,et al.Relationship of serum C3 to fasting insulin,risk factors and previous ischaelnic events in middle-aged men[J].Eur Heart J 2000,21(13):1081-1090.
[39]陈灏珠.实用内科学[M].第11版.北京：人民卫生出版社,2001,1239-1241.
[40]Kim DH,Kim GC,Kim SH,et al.The relationship between the left atrial volume and the maximum P-wave and P—wave dispersion in patjentswith congestive heart failure[J].Yonsei Med J.2007,48(5):810-817.
[41]Maekawa Y,Anzai T,Yoshikawa T,et al. Prognostic significance of peripheral monocytosis after reperfused acute myocardial infarction:Apossible role for left ventricular remodeling[J].J Am Coll cardiol.2002.39(2):241-246.
[42]JOH NIA,McMURRAY J V.WH ITMORE J,etal.Anemia and its relatioilship to clinical outcome in heart failure[J]. Circulation,2004,10:149-154.
[43]AlAH MAD A, RAND W M, MANJUNATH G, etal. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction[J].J Am Coll Cardio 1,2003,38:955-962.
[44]Curtis JP, Sokol SI, Wang Y, et al. The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure[J]. J Am Coll Cardiol,2003,42(4):736-742.
[45]Cohn JN. Structure basis for heart failure:ventricular remodeling and its pharmacological inhibition[J]. Circulation,1995,91(10):2504-2507.
[46]孙伯青.益气活血法治疗充血性心力衰竭的临床研究[J].中国中西医结合急救杂志,2006,13(1)：44-46.
[47]吴时达,吴桐,吴昌碧,等.温阳健心灵口服液治疗收缩功能不全性心力衰竭的临床研究[J].中国中西医结合急救杂志,2001,8(2)：223.
[48]李媛,冠心病慢性心功能不全患者心脏舒缩功能与中医证候相关性研究[D].北京：北京中医药大学,2009：67-82.
[49]Fleiss LJ, Levin B, Paik MC. Statistical Methods for Rates and Pro portions.3rd ed, John Wiley & Sons, Inc., NJ, USA,2003.
[50]李文林,赵国平.数据挖掘技术及其在中医药领域的应用[J].中华医学图书情报杂志,2004,13(6)：4-6.
[1]HORNING MG, MURAKAM IS, HORNING EC. Analyses of phospholipids, ceramides, and cerebrosides by gas chromatography and gas chromatography mass spectrometry[J]. Am J Clin Nutr,1971,24(9):1086-1096.
[2]陈灏珠.内科学[M].北京：人民卫生出版社.1995：263-264.
[3]Peiyuan Yin, Patamu Mohemaiti, Jing Chen, et al. Serum metabolic profiling of Abnormal Savda by liquid chromatography/mass spectrometry[J]. J Chromatography B,2008(5):43.
[4]冒海蕾,徐晏,王斌,等.正交信号校正在正常人血清1H-NMR谱的代谢组分析中的滤噪作用评价[J].化学学报,2007,65(2)：152-158.
[5]廖沛球,张晓字,魏来等.基于NMR的代谢组学方法对硝酸钕急性生物效应的研究[J].分析化学,2008,36(4)：426-432.
[6]Gheorgiade M, Bonow RO. Coronary artery disease and chronic heart failure[J]. Circulation,1998;97:282-289.
[7]Nicholson J K,Lindon J C,Holmes E.'Metabonomics' understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenobiotica,1999,29(11):1181-1189.
[8]Brindle J T, Antti H, Homes E, Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H NMR based metabonomics[J]. Nat Med,2002, 8(12):1439-1444.
[9]Beckwith-Hall BM,Brindle JT,Barton RH,et al.Application of orthogonal signal correction to minimise the effects of physical and biological variation in high resolution 1H NMR spectra of biofluids[J].Analyst,2002,127(10):1283-1288.
[10]Gavaghan CL,Wilson ID,Nicholson JK.Physiological variation in metabolic phenotyping and functional genomic studies:use of orthogonal signal correction and PLS-DA[J].FEBS Lett,2002,530(1-3):191-196.
[11]Kochhar S,Jacobs DM,Ramadan Z,et al.Probing gender-specific metabolism differences in humans by nuclear magnetic resonance-based metabonomics[J].Anal Biochem,2006,352(2): 274-281.
[12]Stella C,Beckwith-Hall B,Cloarec O,et al.Susceptibility of human metabolic phenotypes to dietary modulation[J].J ProteomeRes,2006,5(10):2780-8.
[13]王勇,李春,郭淑贞等.基于CPMG序列慢性心肌缺血血瘀证血清代谢组学分析[J].北京中医药大学学报,2011,34(12),819-822.
[14]刘舒.肝郁证大鼠血清代谢组学的研究[D].广州：广州中医药大学,2009：58-87.
[15]Zimmerli LU, Schiffer E, Zurbig P,et al. Urinary proteomics biomarkers in coronary artery disease[J]. Mol Cell Proteomics,2008;7:290-298.
[16]李宝成,张怡,熊正英.补充酪氨酸对运动能力影响的可能机制[J].北京体育大学学报.2007,30(1)：68.
[17]周军利,黄跃生,党永明,等.甘氨酸对缺血缺氧心肌细胞能量代谢的影响.[J].现代生物医学进展,2008,8(6)：1093-1095
[18]Heys SD, Ashkanani F.Glutamine[J].BrJSurg,1999,86(3):289-290.
[19]蒋小华,李宁,朱维明.肠内免疫营养对手术创伤后机体免疫炎症反应及预后的影响[J].中国实用外科杂志,2004,24(1)：43.
[20]VanderHulst RR,Von Meyenfeldt MF, DeutzNE, etal. Glutamine extraction by the gut is reduced in depleted[corrected]Patients with gastrointestinal cancer[J].Ann Surg.1997;225(1):112-121.
[21]李康,刘蔚,孙福成等.不同内生肌配清除率对冠心病患者预后的影响[J].中国全科医学,2008,11(6)：936.
[22]MA Mamas, W B Dunn, D Broadhurst, etal. Partial reconstruction of myocardial metabolic pathways following analysis of peripheral serum using metabolomics in early cardiac ischemia.[J]. Heart,2010,96(3):13.
[23]巩菊芳,邵邻相,郑孝华,等.大豆磷脂对红细胞膜脂类成分的影响[J].营养学报,2004,26(3)：180-183.
[24]邵邻相.大豆磷脂对小鼠学习记忆及脑内SOD和脂褐素含量的影响[J].浙江师范大学学报(自然科学版),2003,26(3)：275-276.
[25]何新霞,胡燕月,金晓玲.大豆磷脂对大鼠实验性高脂血症的预防[J].浙江师范大学学报(自然科学版),2001,24(2)：191-193.
[26]肖颖,王军波,梁学军,等.富含单不饱和脂肪酸的坚果对高脂血症患者血脂水平的影响[J].中国公共卫生,2002,18(8)：931-934.
[27]YuanJ.M, etal.Fish and shellfish consumption in relation to death from Myocardial infarction among men in shanghai, China[J]. AmJEPidemiol,2001,154:809-816.
[28]BrielM, Ferreira-Gonzalez I, YouJJ, etal.Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality:systematic review and meta-regression analysis[J].BMJ.2009,16;338:b92.
[29]BaranovaAV.AdiPokine genetics:unbalanced Protein secretion by human adipose tissue as a cause of the metabolic syndrome[J].Genetika.2008 Oct;44(10):1338-55.Review
[30]潘明,陈琼.中医体质、病证研究与代谢组学[J]上海中医药杂志,2008,42(6)：53-56.
[31]董飞侠,黄迪,何立,贾伟.Ⅲ期慢性肾病肾阳虚证患者尿液代谢组学特征的研究[J].中华中医药杂志,2008,23(12)：1109-1113.
[32]朱宣宣,王广基,阿基业,等.冠心病中医辨证分型的代谢组学研究[J].中华中医药学刊,2009,27(6)：1267-1269.
[33]Wang Yong, Li Zhongfeng, Chen Jianxin etal. Study of mini-pig serum of coronary heart disease(chronic myocardial ischemia)with syndrome if blood stasis based on nuclear magnetic resonance metavolomics. Chinese Journal of Analytical Chemistry.2011(8),1274-1278.
[34]华何与,贾饪华,张红栓,等.冠心病心绞痛三种血瘀证的血浆代谢组学研究[J].热带医学杂志,2010,10(3)：258-260,279.
[35]简维雄,袁肇凯,黄献平,等.冠心病心血瘀阻证尿液代谢组学的检测分析[J].中医杂志,2010,51(8)：729-732.
[36]刘卫红,张琪,颜贤忠,等.高脂血症及动脉粥样硬化痰瘀演变的代谢组学研究[J].中医杂志.2008,49(8)：738-741.
[37]Expert Panel on Detection,Evaluation,and Treatment of High Blood Cholesterol in Adults.Executive Summary of The Third Report of The National Cholesterol Education Program(NCEP) Expert Panel on Detection,Evaluation,And Treatment of High Blood Cholesterol In Adults(Adult Treatment Panel III) [J].JAMA,2001,285:2486-2497.
[38]Nobuko H, Dileep S.S. Carnitine and Choline Supplementation with Exercise Alter Carnitine Profiles, Biochemical Markers of Fat Metabolism and Serum Leptin Concentration in Healthy Women.[J].J. Nutr.,2003,133(1):84-89.
[39]Kove E.Wakenell, P.Klasing, K.C.Dietary fish oil or lofrin, a 5-liPoxyenase inhibitor, decrease the growth-suppressing effects of coccidiosis in broilerchicks[J].Poultry sci,1997, 76:1335-1363.
[40]严蓓,阿基业,郝海平等.心血瘀阻组与气阴两虚证心肌缺血大鼠模型的代谢组学表征与辨识[J].中国科学C辑：生命科学,2008,38(12)：1143-1151.
[41]马文军；张涛.运动减肥与肉碱的关系[J].武汉体育学院学报,2003,36(5)：52-53.
[42]陈冬梅.虚寒证的证候规律及其代谢组学的研究[D].河北医科大学,2008：35-39.
[43]吕爱平,李德新,崔家鹏,等.脾肾阳虚模型大鼠肝细胞线粒体磷脂组分变化的比较研究[J].中医药学刊.2003,23(1)：78,83.
[44]Nicholson J K, Holmes E, Lindon J C, et al. The challenges of modeling mammalian biocomplexity[J]. Nat Biotechnol,2004,22(10):1268.
[2]X.Guo etal.Prevention of remodeling in congestive heart failure due to myocardial infarction by blockade of the rennin-angiotensin system[J]. Cardiovasc. Ther,2005,3:717-732.
[3]Y.S.Oh,A.Y.Jong and D.T.Kim etal. Spatial distribution of nerve sprouting after myocardial infarction in mice[J].Heart Rhythm,2006,3:728-736.
[4]Thomas P.Cappola MD,ScM Molecular Remodeling in Human Heart Failure[J]. Journal of the American College of Cardiology.2008,2(15):137-138.
[5]Packer M. How should physicians view heart failure? The philosophical and physiological evolution of three conceptual models of the disease[J]. Am J Cardiol,1993,71:3C-11C.
[6]Pepper G,Lee RW. Sympathetic activation in heart failure and its treatment withβ-blockade[J]. Arch Intern Med,1999,159:225-234.
[7]Collucci WS. Molecular and cellular mechanisms of myocardial failure[J]. Am J Cardiol, 1997,80:15L-25L.
[8]Sabbath H,Shrove VG.Apoptosis in heart failure Prog[J].Cardiovasc Dis,1998,40:549-562.
[9]V.J.Dzau,M.Packer,and L.S.Lilly etal.Hollenberg and G.H.Williams, Prostaglandins in severe congestive heart failure relation to activation of the renin-angiotensin system and hyponatremia[J].N Engl J,1984,310:347-352.
[10]D. L.Mann and M.R.Bristow etal.Mechanisms and models in heart failure:the biomechanical model and beyond[J].Circulation,2005,111:2837-2849.
[11]M.R.Bristow,E.M.Gilbert and W.T.Abraham etal.Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure[J].Circulation,1996,94:2807-2816.
[12]G.MERIT-HF Study, Effect of metoprolol CR/XL in chronic heart failure:Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure(MERIT-HF) [J].1999,353:2001-2007.
[13]R.Sethi et al.Dependence of changes in beta-adrenoceptor signal transduction on type and stage of cardiac hypertrophy[J].Appl.Physiol,2007,102:978-984.
[14]P.A.Poole-Wilson et al.Rationale and design of the carvedilol or metoprolol European trial in patients with chronic heart failure[J]. Eur J Heart Fail,2002,4:321-329.
[15]D.F.Goldspink et al.Catecholamine-induced apoptosis and necrosis in cardiac and skeletal myocytes of the rat in vivo:the same or separate death pathways[J].Physiol.2004,89:407-416.
[16]M.Gallego etal.Spironolactone and captopril attenuates isoproterenol-induced cardiac remodelling in rats[J].Pharmacol Res,2001,44:311-315.
[17]M.S.Cuffe et al.Short-term intravenous milrinone for acute exacerbation of chronic heart failure:a randomized controlled trial[J].JAMA.2002,287:1541-1547.
[18]Small KM, Wagoner LE, and Levin AM, et al. Synergistic polymorphisms of betal-and alpha 2C-adrenergic receptors and the risk of congestive heart failure[J].N Engl J Med.2002,347:1135-1142.
[19]Paull JR, Widdop RE et al. Persistent cardiovascular effects of chronic rennin-angiotensin system inhibition following withdrawal in adult spontaneously hypertensive rats[J].J Hypertens 2001,19:1393-1402.
[20]S Oparil et al.Efficacy and safety of combined use of aliskiren and valsartan in patients with hypertension:a randomised,double-blind trial[J].Lancet,2007,370:221-229.
[21]Y.J.Xu et al.Mechanism of the positive inotropic effect of lysophosphatidic acid in rat heart[J]. Cardiovasc Pharmacol Ther,2002,7:109-115.
[22]B.Pitt et al.The effect of spirono lactone on morbidity and mortality in patients with severe heartfailure. Randomized Aldactone Evaluation Study Investigators[J].N Engl J Med,1999,341:709-717.
[23]B.Pitt et al.Eplerenone,a selective aldosterone blocker,in patients with left ventricular dysfunction after myocardial infarction[J].N Engl J Med,2003,348:1309-1321.
[24]翟淑波.充血性心力衰竭发病机制的研究进展[J].临床儿科杂志,2006,10(24)：851-853.
[25]Berkowitz R.B-type natriuretic peptide and the diagnosis of acute heart failure [J].Rev Cardiovasc Med,2004,5(4):3-16.
[26]Abasai Z, Karram T,Ellaham S,et al. Implications of the natriuretic peptide system in the pathogenesis of heart failure:diagnosis and therapeutic importance [J].Pharmacol Ther,2004,102(3):223-241.
[27]Jaime LP, Franc isco JC, Carm en AT, etal.Accuracy of B-type natriuretic peptide levels in the diagnosis of left ventricular dysfunction and heart failure:A systematic review[J]. EurJHeart Fai,2006,8:390-399.
[28]Yoshimura M, YasueHogava H. PathoPhysiological significance and Clinical application of ANP and BNP in patients with heart failure[J]. Can J Physiol Pharmaeol,2001,79:730-735.
[29]Ishi Junich, Rinsho B.Clinical utility of NT-proBNP, a new biomarker of cardiac function and heart failure [J]. J ClinPatho,2008,56(4):316-321.
[30]Michele E, Claudio P, Concetta P, et a.l Comparison of Brain Natriuretic Peptide (BNP) and N-Terminal ProBNP for Early Diagnosis of Heart Failure[J].ClinChem,2007,53:1289-1297.
[31]Manowitz N R, Mayor G H, Klepper M J, etal. Hypothyroidism and thyroidsike syndrome in patients with moderate to severe congestive heart failure[J]. Am J Ther,1996, 3(1):797-801.
[32]Koglin J, Pehlivanlj S, Schwaiblmair M, etal. Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure [J].J Am CollCardiol,2001,38 (5):1934-1941.
[33]薛礼美,陈晓虎等.CHF的神经内分泌激素、细胞因子变化的研究进展[J].医学综述2004,10(3)：146-150.
[34]Han W, Chartier D, L i D, etal. Ionic remodeling of cardiac purkinje cells by congestive heart failure[J]. Circulation,2001,104 (17):2095-2100.
[35]Verkerk AO, Veldkamp MW, Baartscheer A, et al. Ionic mechanism of delayed after depolarizations in ventricular cells isolated from human end stage failing hearts[J]. Circulation,2001,104 (22):2728-2733.
[36]Watanbe T, YamakiM, Yamauchi S, et al. Regional prolongation of ARI and altered restitution properties cause ventricular arrhythmia in heart failure[J]. Am JPhysiol,2002,282 (1):H218.
[37]Dipla K,Mattiello JA,Margulies K,et al.The sarcop lasmic reticulum and Na+-Ca2+ exchanger both contribute to the Ca2+ transient of failing human ventricular myocytes[J].Circ Res,1999,84:435-444.
[38]M.Yano et al.FKBP12.6-mediated stabilization of calcium-release channel(ryanodine receptor)as a novel therapeutic strategy against heart failure[J].Circulation,2003;107:477-484.
[39]S.E.Lehnart et al.Novel targets for treating heart and muscle disease:stabilizing ryanodine receptors and preventing intracellular calcium leak[J].Curr Opin Pharmacol,2007,7:225-232.
[40]M.Asahi et al.Regulation of sarco(endo)plasmic reticulum Ca2+ adenosine triphosphatase by phospholamban and sarcolipin:implication for cardiac hypertrophy and failure[J].Trends Cardiovasc Med,2003,13:152-157.
[41]A.Ghatak,M.J.Brar and A.Agarwal et al.Oxy free radical system in heart failure and therapeutic role of oral vitamin E[J].Int J Cardiol,1996,57:119-127.
[42]F.Giordano,Oxygen,oxidative stress,hypoxia,and heart failure[J].J Clin Invest,2005, 115:500-508.
[43]Ghosh MC, Wang X, eta 1.Regulation of caleineurinby oxida-five stress [J].Methods Enzymol,2003,366:289-304.
[44]M.Keith,A.Geranmayegan and M.J.Sole etal.Increased oxidative stress in patients with congestive heart failure[J].J Am Coll Cardiol,1998,31:1352-1356.
[45]F.Qin et al.Inhibition of NADPH oxidase reduces myocardial oxidative stress and apoptosis and improves cardiac function in heart failure after myocardial infarction,Free Radic[J].Biol Med,2007,43:271-281.
[46]Y.T.Sia et al.Beneficial effects of long-term use of the antioxidant probucol in heart failure in the rat[J].Circulation,2002,105:2549-2555.
[47]I.Dalle-Donne,D.Giustarini,and R.Colombo et al.Protein carbonylation in human diseases[J].Trends Mol Med,2003,9:169-176.
[48]Cristina Banfi and Maura Brioschi et al,Oxidized proteins in plasma of patients with heart failure:Role in endothelial damage[J]. European Journal of Heart Failure,2008,10(3):244-251.
[49]C.D.Rollo,J.Carlson and M.Sawada,Accelerated aging of giant transgenic mice is associated with elevated free radicals process[J].Can J Zool,1996;74:606-620.
[50]Stefan Neubauer.The Failing Heart-An Engine Out of Fuel[J].N Engl Jmed,2007,356:1140-51.
[51]V.Lionetti et al.Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure[J].Cardiovasc Res,2005;66:454-461.
[52]L.A.Nikolaidis et al.Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion[J].Circulation,2004,109:962-965.
[53]I.Thrainsdottir etal.Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure[J]. Diab Vasc Dis Res,2004,1:40-43.
[54]S.Schmidt-Schweda and C.Holubarsch,First clinical trial with etomoxir in patients with chronic congestive heart failure[C].Clin.Sci.(Lond.),2000,99:27-35.
[55]陈齐红,覃数.肿瘤坏死因子-α和充血性心力衰竭.心血管病学进展,2004,25(2)：89-91.
[56]M.Sun et al.Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state[J]. Circulation,2007,115:1398-1407.
[57]M.Sun et al.Excessive tumor necrosis factor activation after infarction contributes to susceptibility of myocardial rupture and left ventricular dysfunction[J].Circulation,2004,110:3221-3228.
[58]Feldm an AM, Com bes A and W agner D,etal.The role of tumor necrosis factor in the pathophysiology of heart failure[J].J Am CollCardiol,2000,35(3):537-544.
[59]Levine B, KaLman, Maver L et al. Elevated circulation levels of tumor necrosis factor in severe chronic hear failure[J].N Engl J Med,1990,323(4):236-241.
[60]邱飞,王礼深.肿瘤坏死因子-α与心力衰竭的研究进展[J].国外医学药学分册,2003,30(6)：326-330.
[61]Kadokami T, Frye C, Lemster B, et al. Anti-tumor necrosis factor-aAntibody limits heart failure in a transgenic model [J]. Circulation,2001,104 (10):1094-1097.
[62]B radham WS,Moe G,Wendt KA, et al. TNF-alpha and myocardialmatrix metallo proteinases in heart failure:relationship to LV remodeling[J]. Am J PhysiolHeart Circ Physiol, 2002,282(4):H1288-H1295.
[63]Li Y Y,Mctierman CF, Feldman AM. IL-1 beta alters the expression of the receptor tyrosine kinase generEphA3 in neonatal rat cardiomyocytes[J]. Cardiovasc Res,1999,42: 162-172.
[64]Shioi T,Matsumori A, Kihara Y, et al. Increased exp ression of interleukin-1βand monocyte chemotactic and activating factor/monocyte chemo attractant protein 1 in the hypertrophied and failing heart with pressure overload [J]. CircRes,1997,81 (5):664-671.
[65]Torre-Amione G, Kapadia S, Benedict C, et al.Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction; a report from the studies of left ventricular dysfunction(SOLVD). J Am Collcardiol,1996,27:1202-1206.
[66]刘传亮,刘向群.白细胞介素与左心室收缩功能关系探讨[J].山东医药,2002,42(23)：48-49.
[67]Givertz MM, Collueei WS. New targets for heart failure therapy:endothelin, inflammatory, cytokines. oxidative stress[J].Lancet.1998,352(Suppl I):134-138.
[68]HocherB, George I, Rebstock J, etal. Endothelin system2dependent cardiac remodeling in renovascular hypertension [J]. Hypertension,1999,33 (3):816-822.
[69]Mulder P,Boujedanini H, Richard V, etal. Selective endothelin A versum combined endothelin-A/endothelin-B receptor blockade in rat chronic heart failure[J]. Circulation,2000, 102 (5):491-493.
[70]Martin P,BoujedainiH, RichardV, et al. Effect of a highly selective endothelin-converting enzyme inhibitor on cardiac remodeling in rats after myocardial infarction[J].Cardiovasc Pharmacol,2000,36 (5 supp 11):S367-S370.
[71]Pechanova O,Bernatova I, Pelouch V, etal. L-NAME-induced protein remodeling and fibrosis in the rat heart [J]. Physiol Res,1999,48 (5):353-362.
[72]K.T.Weber et al.Angiotensin Ⅱ and extracellular matrix homeostasis[J].Biochem Cell Biol, 1999,31:395-403.
[73]F.G.Spinale,M.L.Coker and S.R.Krombach et al.,Matrix metalloproteinase inhibition during the development of congestive heartfailure:effects on left ventricular dimensions and function[J].Circ Res.1999;364-376.
[74]J T Peterson,H.Hallak and L Johnson etal.,Matrix metalloproteinase inhibition attenuates left ventricular remodeling and dysfunction in a rat model of progressive heart failure[J].Circulation,2001,103:2303-2309.
[75]Spninale FG, Coker ML, Heung LJ, etal. A matrix metalloproteinase induction/ activation system exists in the human left ventricular myocardium and is up regulated in heart failure[J].Circulation,2000,102:1944-1949.
[76]Massie BM, Shah NB. Evolving trends in the epidemiologic factors of heart failure: rational for preventive strategies and comprehensive disease management [J]. Am Heart J 1997,133:703-712.
[77]American Heart Association.2002 Heart and Stroke Statistical Updata[C].Dallas,TX American HeartAssociation,2002:19.
[78]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.全国世纪之交心力衰竭学术研讨会纪要[J].中华心血管病杂志,2002,30(1)：226.
[79]KannelWB, Ho K, Thom T. Changing epidemiological features of cardiac failure[J]. Br Heart J,1994,72 (supp 1):S3-S9.
[80]上海市心力衰竭调查协作组.上海市1980、1990、2000年心力衰竭住院患者流行病学及治疗状况调查.中华心血管病杂志,2002,30(1)：24-27.
[1]Gu DF, Huang GY, He J, Wu XG, Duan XF. Investigation of prevalence and distributing feature of chronic heart failure in Chinese adult population[J]. Zhonghua Xin Xue Guan Bing Za Zhi,2003; 31 (1):326.
[2]王娟,陈婵,张鹏等.口服中药治疗慢性心衰随机对照试验的系统评价[J].中华中医药杂志,2011,26(12)：2830-2840.
[3]吴红金,袁国会.心力衰竭中西医结合治疗学[M].北京：清华大学出版社,2008：6.
[4]谭璐芸.郭维琴治疗心力衰竭经验介绍[J].云南中医学院学报,2000,(23)2：43.
[5]赖旭峰,单赤军.邓铁涛教授从脾论治慢性充血性心力衰竭经验[J].河北中医,2001,12(23)12：909.
[6]周仲英等.益阴助阳活力血通脉法治疗充血性心力衰竭的临床研究[J].南京中医药大学学报,1998,12(3)：34.
[7]薛长玲.董燕平治疗慢性心力衰蝎经验[J].中医药学刊,2004,4(17)：2250.
[8]曹雪滨,胡元会,王士雯.充血性心力衰竭辨证分型与血管活性的关系[J].辽宁中医杂志,1999,26(10)：441-42.
[9]郑筱英.中药新药临床研究指导原则[M].中国医药科技出版社,2002,5(1)：79-80.
[10]朴勇洙,冯大鹏,蔡宏宇.充血性心力衰竭的中医概述[J].中华实用中西医杂志,2003,3(16)：479.
[11]陈可冀,廖家祯,肖镇祥.心脑血管疾病研究[M].上海：上海科学技术出版社,1998：28.
[12]黄永生.心衰论治.湖南中医药导报,2000,6(9)：3.
[13]杨培君,杨磊.充血性心力衰竭的中医证治概要[J].陕西中医学院学报,2003,25(1)2-5.
[14]腾国华,程君.心衰的病因病机及其辨证轮治[J].中医药学刊,2004,22(7)：1331.
[15]狄灵,梁君昭.心力衰竭辨证的临床思路与方法[J].中医杂志,2002,43(1)：67.
[16]黄平东,罗懿明,黄衍寿等.充血性心力衰竭中医证型特征及其演变规律的临床观察[J].中西医结合心脑血管病杂志,2003,1(12)：685-686.
[17]王振涛.充血性心力衰竭辩治体验[J].四川中医,2005,23(6)：9-10.
[18]屈营,张明谦.辨证治疗慢性心衰的临床体会[J].中医药学刊,2005,23(5)：951.
[19]张瑞华,焦增绵,马丽红.慢性充血性心力衰竭的中医辨证论治[J].中国医药学报,2002,17(7)：440-441.
[20]许心如.心力衰蝎的中医辨证施治[J].北京中医,1959,(3)：10.
[21]赵淳.慢性心力衰竭现代治疗进展及中医诊治思路探讨[J].中国中医急症2006.2(15)：158-163.
[22]缪灿铭.心力衰竭胆固醇水平与中医辨证候及病变关系的临床探讨[J].中医研究,2003,28(3)：28
[23]梁东辉.充血性心力衰竭的辨证分析及中西医结合治疗规律初探[J].实用中西医结合杂志,1997,10(11)：1069.
[24]贺泽龙,郭振球.充血性心力衰竭中医证候的临床回顾性调查研究[J].湖南中医学院学报,2003,23(5)：33-36.
[25]周英.心血管病表现心虚证患者左心舒张功能观察[J].中国中西医结合杂志,1995,15(1)：13-14.
[26]苗阳,赵文静,荆鲁,等.中西医结合治疗慢性心力衰竭的回顾性分析[J].中国中西医结合杂志,2008,28(5)：406-409.
[27]沈建平,王德春.充血性心力衰竭心虚证与心功能关系的探讨[J].辽宁中医杂志,1997,24(6)：245.
[28]蒋梅先,彭鹏,唐静芬等.心肾同病等病机与充血性心力衰竭循环激素的关系[J].上海中医药大学学报,2000,14(1)：27-29.
[29]周杰.高晓玲等.充血性心力衰竭患者心钠素与中医辨证分型相关性的临床研究[J].中 国中西医结合杂志,2003,3(16)：1322-1 324.
[30]曹雪滨,王士雯等.充血性心力衰竭中医辨证分型与心功能的关系[J].新中医,2000,32(2)：37-39.
[31]曹雪滨,胡元会等.充血性心力衰竭中医辨证分型与活性肽的关系[J].辽宁中医杂志,1999,26(10)：441-442.
[32]潘光明,邹旭,林晓忠等.心力衰竭患者脑钠肽与中医辨证分型相关性的临床研究[J].新中医,2006,38(4)：33-34.
[33]陈国通,陈永忠,邹襄,B型利钠肽与慢性心力衰竭中医证型的关系[J].中外医疗.2010,29(24)：53-54.
[34]邢晓博,刘福颂,张丙印.氨基末端B型脑钠肽前体、高敏C反应蛋白与脾肾阳虚型慢性心力衰竭的相关性探讨[J].中国医药导报,2011,8(32)：31-32.
[35]董其美,顾景淡,等.心脏病的中医虚证分型与左心功能关系的探讨[J].中西医结合杂志,1985,(5)：148-150.
[36]周杰,高晓玲,张宝州,等.充血性心力衰竭患者中医辩证分型与左心室功能不全的相关性研究[J].中医杂志.2003,44(8)：615-616.
[37]郑关毅,刘贵灿.心气虚患者左心室功能的多谱勒超声心动图[J].实用中西医结合杂志,1997,10(3)：1278.
[38]邓铁涛.中医诊断学[M].上海：上海科技出版社,1984.
[39]中国中西医结合研究会虚证与老年病专业委员会.中医虚证辨证参考标准[J].中西医结合杂志,1986,6(10)：598.
[40]中国中西医结合研究会活血化瘀专业委员会-血瘀证诊断标准[J].中西医结合杂志,1987,7(3)：129.
[41]蔡晓丽.慢性心力衰竭各证型与甲状腺激素水平的特征研究[D].广州中医药大学,2011：10-11.
[42]徐家新,钟志戎.充血性心力衰竭患者中医辨证与甲状腺激素变化的相关性研究[J].河北中医,2004；26(10)：732-733.
[43]缪灿铭,李雪山,林凯旋等.甲状腺激素水平与心力衰竭的功能分级及中医辨证的关系[J].光明中医,2003；18(105)：2-5.
[44]周杰,高晓玲.充血性心力衰竭中医辨证分型与心功能参数及甲状腺激素相关性的临床研究[J].中国中西医结合杂志,2004;,24(10)：872-874.
[45]薄艳丽.慢性心力衰竭阳虚证型与甲状腺激素关系的研究[D].广州：广州中医药大学,2009：48-54.
[46]张启华.充血性心力衰竭患者血清C即水平的变化及与心功能的关系[J].中外医疗,2008,17：37.
[47]陈瑞,廖远芬,梁凤霞等.充血性心力衰竭心气、阳虚证与肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-10的关系[J].中国中医药信息杂志,2003,10(8)：14-16.
[48]陈瑞,廖远芬,梁凤霞等.充血性心力衰竭心气(阳)虚证与肿瘤坏死因子-a、白细胞介素-6关系的探讨[J].湖北中医杂志,2003,25(5)：10-11.
[49]万智,宋刚.心力衰竭心肾阳虚／气阴两虚型与白细胞介素-6的关系研究[J].新疆中医药,25(3)：16-18.
[50]刘革命,熊尚全,马成富.慢性心力衰竭中医辨证分型与血浆NO及TNF-a含量的关系[J].山东中医杂志,2004,23(2)：71-72.
[51]商俊芳,周杰,高晓玲,等.充血性心力衰竭中医辨证分型与左心功能不全及心钠素、内皮素的相关性研究[J].中国中医药信息、杂志,2010,17(9)：23-36.
[52]郭跃进,郑春盛,詹萍.慢性心力衰竭血清sFas、外周血单个核细胞凋亡与心功能及中医证型的关系[J].福建中医学院学报,2005,15(6)：1-3.
[53]朱珍道,林求诚.心肾阳虚型充血性心力衰竭患者红细胞内ATP酶、SOD、钠钾钙镁及血清LPO的变化及其相互关系[J].实用中西医结合杂志,1998,11(2)：131-132.
[54]韩丽华,王振涛,牛晓亚等.充血性心衰阳虚证与免疫功能及血流变的关系[J].河南中医,1996,16(6)：344-346.
[55]殷鑫,王相东,刘晓燕.循证医学对四诊客观化研究的启示[J].中国中医基础医学杂志,2006,12(4)：299-300.
[56]邱德有,吴小红,黄璐琦.现代生命科学技术对中医药发展的影响[J].世界科学技术-中医药现代化,2001；3(2)：12-16.
[57]王永炎,张志斌.再议完善辨证方法体系的几个问题[J].天津中医药,2007,,24(1)：1-4.
[1]颜贤忠,赵剑字,彭双清,廖明阳.代谢组学在后基因时代的作用[J].波谱学杂志,2004,21(2)：263-270.
[2]许国旺,杨军.代谢组学及其研究进展[J].色谱,2003,21(4)：316-320.
[3]李晶,吴晓健,刘吕孝,元英进.代谢组学研究中数据处理方法的应用[J].药学学报,2006,41(1)：47-53.
[4]HORNING MG, MURAKAM IS, HORNING EC. Analyses of phospholipids,ceramides, and cerebros ides by gas chromatography and gas chromatography mass spectrometry[J]. Am J Clin Nutr,1971,24(9):1086-1096.
[5]NICHOLSON JK,LINDON JC,HOLMES E. Metabonomics:understanding the metabolic responses of living systems to patho-physiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenbiotica,1999,29(11):1181-1189.
[6]NICHOLSON JK,BOLLARD ME,LINDON JC, etal.Metabonomics:a platform for studying drug toxicity and gene function[J].Nat Rev Drug Discov,2002,1(2):153-162.
[7]BRINDLE JT,ANTT IH,HOLMES E,etal.Rapid and non invasive diagnosis of the presence and severity of coronary heart disease using 1H-NMR-based metabonomics[J]. NatMed, 2002,8(12):1439-1444.
[8]WATERS NJ,HOLMES E,WATERFIELD CJ,etal. NMR and pattern recognition studies on liver extracts and intact livers from rats treated with a-naphthy lisothiocyanate [J].BiochemPharmacol,2002,64(1):67-77.
[9]HOLMES E,ANTT IH. Chemo metric contributions to the evolution of metabonomics: mathematical solutions to characterizing and interpreting complex biological NMR spectra[J].Analyst,2002,127(12):1549-1557.
[10]FIEHN O. Metabolic networks of Cucurbita maxima phloem[J].Phytochemistry,2003, 62(6):875-886.
[11]朱航,唐惠儒,张许,刘买利.基于NMR的代谢组学研究[J].化学通报.2006,69(7)：1-9.
[12]HOLMES E,NICHOLSON JK,TRANTER G.Metabonomic characterization of genetic variations in toxicological and metabolic responses using probabilistic neural networks[J].ChemResToxicol,2001,14(2):182-191.
[13]KEUN HC,EBBELS TMD,ANTT IH, etal.Analytical reproducibility in 1H NMR-Based metabonomic urinalysis[J].ChemResToxicol,2002,15(11):1380-1386.
[14]LINDON JC,HOLMES E,NICHOLSON JK,Recent developments and applications of NMR-based metabonomics[J].Chin J MagnResonance,2006,23(1):101-127.
[15]赵剑宇,颜贤忠.基于核磁共振的代谢组学研究进展[J].国外医学药学分册.2004,31(5)：308-312.
[16]刘昌孝.代谢组学的发展于药物研究开发[J].天津药学.2005,17(2)：1-6.
[17]Nicholson JK, Wilson ID. High resolution proton magnetic resonance spectroscopy of biological fluids[J].Prog Nucl MagRes Spectrosc,1989,21(4):449. [18]TangH, WangY, Nicholson JK, etal. Use of relaxation-edited one-dimensional and two dimensional nuclear magnetic resonance spectroscopy to improve detection of small Metabolites in blood plasma[J].Anal Biochem,2004,325(3):260.
[19]Hall BM, Thompson NA, Nicholson JK, etal. A metabonomic investigation of heap to toxicity using diffusion-edited'HNMR spectroscopy of blood serum[J].Analyst,2003,128(7): 814.
[20]Gamache PH,Meyer DF,Granger MC,etal. Metabolomic applications of Electro chemistry/massspectrometry[J].J AmSocMassSpectrom,2004,15:1717.
[21]陈慧梅.代谢组学及其研究方法和应用[J].肾脏病与透析肾移植杂志,2005,14(1)：59-63.
[22]HOLMES E,N ICHOLLS AW,LINDON JC,etal.Chemo metric models for toxicity classification based on NMR spectra of biofluids[J].Chem ResToxicol,2000,13(6):471-478.
[23]ROBERTSON DG,RE ILYMD,SIGLER RE, etal.Metabonomics:evaluation of nuclear magnetic resonance(NMR) and pattern recognition technology for repid in vivo screening of liver and kidney toxicants[J].ToxicolSci,2000,57(2):326-337.
[24]LU G,WANG JS,ZHAO XJ,etal.Study on gender difference based on metabolites in urine by ultra high performance liquid chromatography/time of flight mass spectrometry[J].Chin J Chromatogr,2006,24(2):109-113.
[25]徐旻,林东海,刘昌孝.代谢组学研究现状与展望[J].药学学报,2005,40(9)：769-774.
[26]BECKONERT O, BOLLARD ME, EBBELS TMD, etal. NMR based metabonomic toxicity classification:hierarchical cluster analysis and K-nearest-neighhour approach [J]. Anal Chim Acta,2003,490(1-2):3-15.
[27]Nicholls AW, Nicholson JK, Haselden JN, etal. A metabonomic approach to the investigation of drug-induced phospholipidosis:an NMR spectroscopy and pattern recognition study [J], Biomarkers,2000,5(6):410-423.
[28]Griffin JL, Bollard ME. Metabonomics:Its potential as a tool in toxicology for safety assessment and data integration[J].Curr Drug Metab,2004,5:389-398.
[29]Nicholson JK, Connelly J, Lindon JC, et al. Metabonomics:a platform for studying drug toxicity and gene function[J].Nature,2002,1:153-161.
[30]Slim RM, Robertson DG., Albassam M, etal. Effect of dexamethasone on the metabonomics profile associated with phosphodiesterase inhibitor-induced vascular lesions in rats[J], Toxicol Appl Pharmacol,2002,183:108-116.
[31]Lehman Mckeeman LD, Car BD. Metabonomics:Application in predictive and mechanistic toxicology[J]. Toxicol Pathol,2004,32(Suppl.2):94-95.
[32]Azmi J, Griffin JL, Shore RF, et al. Chemometric analysis of biofluids following toxicant induced hepatotoxicity:A metabonomic approach to distinguish the effects of 1-naphthylisothiocyanate from its products[J]. Xenobiotica,2005,35(8):839-852.
[33]Warne MA, Lenz EM, Osborn D, et al. An NMR-based metabonomic investigation of the toxic effects of 3-trifluoromethyl-aniline on the earthworm Eisenia veneta[J]. Biomarkers,2000,5(1):56-72.
[34]Shockcor JP, Holmes E. Metabonomic applications in toxicity screening and disease diagnosis[J].CurrTopMed Chem,2002,2:35-51.
[35]Mar E Bollard, Elizabeth G. Stanley, John C. Lindon, Jeremy K. Nicholson, Elaine Holmes. NMR-based metabonomic approaches for evaluating physiological influences in biofluid composition[J]. NMR Biomed,2005,18:143-162.
[36]Brindle J T, Antti H, Homes E, Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H NMR based metabonomics[J]. Nat Med,2002, 8(12):1439-1444.
[37]Harald Mischak, Joshua J.Coon, Jan Novak, Eva M. Weissinger, Joost Schanstra,and Anna F. Dominiczak, Capillary electrophoresis-mass spectrometry as a powerful tool in biomarker discovery and clinical diagnosis:an update of recent developments[J].Mass Spectrom Rev.2009,28(5):703-724
[38]Zimmerli LU, Schiffer E, Zurbig P, Kellmann M, Mouls L, Pitt A, Coon JJ, Schmiederer RE, Mischak H, Peter K, Kolch W, Delles C, Dominiczak AF. Urinary proteomics biomarkers in coronary artery disease[J]. Mol Cell Proteomics,2008,7:290-298.
[39]Snell-Bergeon JK, Maahs DM, Ogden LG, Kinney G Hokanson JE, Schiffer E, Rewers M, Mischak H. Evaluation of urinary biomarkers for coronary artery disease, diabetes, and diabetic kidney disease[J]. Diabetes Technol Ther,2009; 11(1); 1-9.
[40]Martin JC, Canlet C, Delplanque B,etal.'HNMR metabonomics can differentiate the early atherogenic effect of dairy products in hyperlipidemichamsters[J], Atherosclerosis,2009,206:127-133.
[41]Yang J, Xu GW, Hong QF, et al. Discrimination of type 2 diabetic patients from healthy controls by using metabonomicsmethod based on their serum fatty acid profiles[J].JChromatogrB,2004,813:53-58.
[42]Hodavance MS, Ralston SL, Pelczer I. Beyond blood sugar:the potential of NMR-based metabonomics for type 2 human diabetes, and the horse as a possible model[J].Anal Bio anal Chem,2007,387:533-537.
[43]Whitehead TL, Emmons TK. Applying in vitro NMR spectroscopy and 1H NMR metabonomics to breast cancer characterization and detection[J],Prog Nucl Magn Reson Spectrosc,2005,47:165-174.
[44]Yang J, Xu GW, Zheng YF, et al. Diagnosis of liver cancer using HPLC-based metabonomics avoiding false-positive result from hepatitis and hepatocirrhosis diseases[J].JChromatogrB,2004,813:59-65.
[45]Li F, Lu X, Liu H, etal.A pharmacometabonomic study on the therapeutic basis and metabolic effects of Epimediambrevicornum Maxim on hydrocortisone induced rat using UPLC-MS[J].BiomedChromatogr,2007,21 (4):397-405.
[46]王喜军,孙文军,孙晖,等.CC14诱导大鼠肝损伤模型的代谢组学及茵陈蒿汤的干预 作用研究[J].世界科学技术：中医药现代化,2006,8(6)：101-106.
[47]Kim HK, Choi YH, Erkelens C, etal.Metabolic fingerprinting of Ephedra species using 1H-NMR spectroscopy and principal component analysis[J].ChemPharmBull,2005,53(1):105-109.
[48]Susan J Murch, H P Vasantha Rupasinshe, D Goodenowe et al. A metabolomic analysis of medicinal diversity in Huangqin (Scutellaria baicalensis Georgi)genotypes:discovery of novel compounds[J].Plant Cell Repots,2004,23(6):419-425.
[49]齐炼文,李萍,赵静.代谢组学与中医药现代研究[J].世界科学技术-中医药现代化,2008,8(6)：79-86.
[50]樊夏雷,刘文英,王广基等.基于GC/TOF/MS的关木通肾毒性代谢组学研究[J].毒理学杂志,2007,21(4)：323.
[51]张杰,李浸.关于中医证候物质基础研究路径的思考[J].中国中医基础医学杂志,2007,13(5)：394-395.
[52]申维玺.论中医“证本质”的科学内涵[J].中国中医基础医学杂志,2001,7(6)：10-14.
[53]吴巧凤,颜贤忠,唐勇,等.代谢组学在我国中医药领域的应用[J].四川中医,2008,26(3)：7-9.
[54]董飞侠,黄迪,何立,贾伟.Ⅲ期慢性肾病肾阳虚证患者尿液代谢组学特征的研究.中华中医药杂志(原中国医药学报),2008,23(12)：1109-1113
[55]Wang Yong, Li Zhongfeng, Chen Jianxin etal. Study of mini-pig serum of coronary heart disease(chronic myocardial ischemia)with syndrome if blood stasis based on nuclear magnetic resonance metavolomics.Chinese Journal of Analytical Chemistry.2011(8),1274-1278.
[56]Li L,Wang JN,Ren JX,et al.Metabonomics analysis of the urine of rats with Qi deficiency and blood stasis syndrome based on NMR techniques中国科学通报(英文版),2007,52(22)：3068-3073.
[1]中华医学会心血管病学分会.慢性心力衰竭诊断治疗指南[J].中华心血管病杂志,2007,35(12)：1076-1095.
[2]中国中西医结合研究会活血化瘀研究委员会.血瘀证诊断标准[J].中西医结合杂志,1987,7(3)：129.
[3]沈自尹.中医虚证辨证参考标准[J].中西医结合杂志,1989,9(2)：11.
[4]朱文峰,王永炎.中医临床诊疗术语-证候部分[M].北京：中国标准出版社,1997：8-85.
[5]徐迪华,徐剑秋.中医量化诊断[M].南京：江苏科学技术出版社,1997：1-152.
[6]吴焕林,阮新民,罗文杰,等.319例冠心病患者证型分布聚类分析及证型诊断条件的确立[J].中国中西医结合杂志,2007,27(7)：616-617.
[7]欧爱华,罗翌,严夏,等.SARS与急性上呼吸道感染中医证候分型及指标数量化方法的探讨[J].中国卫生统计,2006,23(4)：309-311.
[8]Kannel WB, Ho K, Thom T. Changing epidemiological features of cardiac failure[J]. Br Heart J,1994,72 (supp 1):S3-S9.
[9]刘莹,陈庆伟,吴庆,等.老年人增龄、性别差异与冠心病的相关性研究[J].重庆医科大学学报,2010,35(3)：403-407.
[10]顾东风,黄广勇,何江,等.中国心力衰竭流行病学调查及其患病率[J].中华心血管病杂志,2003,31(1)：3-6.
[11]KalonKLH, JoanLP, WilliamBK, etal.The epidemiology of heart failure:TheFramingham Study[J].JAmCollCardiol,1993,22(4):6A-13A.
[12]中国心血管健康多中心合作研究组.中国心力衰竭流行病学调查及其患病[J]中华血管病杂志,2003,31(1)：3-6.
[13]谭璐芸.郭维琴治疗心力衰竭经验介绍[J].云南中医学院学报,2000,(23)2：43.
[14]曹雪滨,胡元会,王士雯.充血性心力衰竭辨证分型与血管活性的关系[J].辽宁中医杂志,1999,26(10)：441-42.
[15]陈婵.基于数据挖掘的冠心病心力衰竭中医证候因素及生物学基础研究[D].北京：北京中医药大学,2010：35-45.
[16]文川,程伟.206例冠心病心纹痛患者问诊资料与中医辨证关系的探讨[J].湖北中医杂志,2002,(10)：3
[17]王娟,陈婵,张鹏等.口服中药治疗慢性心衰随机对照试验的系统评价[J].中华中医药杂志,2011,26(12)：2830-2840.
[1]邱德有,吴小红,黄璐琦.现代生命科学技术对中医药发展的影响[J].世界科学技术-中医药现代化,2001；3(2)：12-16.
[2]Ezekowitz JA, M calister FA, Arm strong PW, etal.Anemia is common in heart failure and is associated with poor outcomes[J]. Circulation,2003,107:223-225.
[3]VanderMeer P, Voors AA, Lipsic E, etal Erythropoietin in cardio vascular diseases[J]. EurHeart,2004,25:285-291.
[4]SILVERBERG D S, WEXLER D, BLUM M, et al.The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe,resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations [J]. JAmCollCardiol,2000,35:1737-1744.
[5]TANNER H, MOSCH OVITI S G, KUSTER GM,et al. The prevalence of anemia in chronic hear t failure[J]. Int JCardiol,2002,86:115-121.
[6]MACDOUGALL I C. T he role of ACE inhibitors and angiotensin receptor blockers in the response to epoetin[J]. Nephr ol Dial Transplant,1999,14:1836-1841.
[7]CROMIE N, LEE C, STRUTH ERS AD. Anemia in chronic heart failure:What is its frequency in the UK and its underlying cause? [J]. Heart,2002,87:377-378.
[8]McalisterFA,Stewart S,Ferrua S,etal. Multi disciplinary strategies for the management of heart failure patients at high risk for admission:a systematic review of randomized trials[J].J Am Collcardiol,2004,44(4):810-819.
[9]曹雪滨,胡元会,王士雯.充血性心力衰竭辨证分型与血管活性的关系[J].辽宁中医杂志,1999,26(10)：441-42.
[10]Anand R, LatiniR, MassonS, etal.C-Reactive Protein in Heart Failure Value and the Effect of Valsartan[J]. Circulation,2005,112:1428-1434.
[11]Anand S, YenJ, FlreaVG, etal. Prognostic of neutron philandlymPhoeyteeounts in heart failure:results from Val-HeFT Program and abstracts from the American College of Cardiology 53rd AnnualSeientifieSession;Mareh7-10,2004;NewOrleansLouisiana. Abstract.1163-1211.
[12]张道杰.F-800血液分析仪对血瘀证的诊断价值[J].山东中医学院学报1995；19(5)：325-326
[13]刘正兴,王青.低T3综合症与充血性心力衰竭[J].疑难病杂志,2002,1(1)：54-65.
[14]CHEN PU, HE SH,WANG LH, et al. Relation between thyroxine and primary disease in congestive heart failure children [J].Chin J Emerg Med,2003,12:191-192.
[15]周杰,高晓玲,张宝州.充血性心力衰竭中医辨证分型与心功能参数及甲状腺激素相关性的临床研究[J].中国中西医结合杂志,2004,24(10),872-874.
[16]Horwich TB, Hamilton MA, MacLellan WR. et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure[J]. J Card Fail. 2002,8(4):216-224.
[17]ZOCCAL I C, MAIO R, MALLAMACI F. Uric acid and endothelial dysfunction in essential hypertension[J].Am Soc Nephrol,2006,17:1466-1471.
[18]SANCHEZ2LOZADA L G, NA KA GAWA T, KANG D H, etal. Hormonal and cytokine effect s of uric acid[J].Curr Opin Nephrol Hypertens,2006,15:30-33.
[19]L EYVA F, AN KER S, SWAN J W, etal. Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure [J]. Eur Heart J,1997,18:858-865.
[20]沈倩波,许顶立,高锦雄等.睡眠呼吸障碍对高血压患者血尿酸的影响[J].心肺血管病杂志,2006,25(3)：150-152.
[21]VIAZZI F, PARODI D, L EONCINI G, et al. Serum uric acid and target organ damage in primary hyper-tension[J].Hypertension,2005,45:991-996.
[22]FAN G J, ALDERMAN M H. Serum uric acid and cardiovascular mortality the N HANES I Epidemiologic follow-up study,1971-1992 [J]. JAMA,2000,283:2404-2410.
[23]RdkerPM, RifaiN, CiearfieldM, etal.Measurement of C-reactive protein for the targeting of stain therapy in the Primary Prevention of acute coronary events[J].NEnglJMed, 2001,82(1):256-267.
[24]LatinIR, AnandS, MaSSonS,etal. C-reactive protein in 4202 patients with moderate heart failure in Val-HeFT[J]. EurJHeartFail(Suppl),2004:3:112-114.
[25]SakataY, YamamotoK, ManoT, etal.Activation of matrix metal-proteinases-Proceeds left ventricular remodeling in hypertensive heart failure rats:its inhibition as a Prima-effect of angiotensin-everting enzyme inhibitor[J].Circulation,2004:109(17):21-43.
[26]Alons MarlinezJL, Liorente DiezB, Eehegara AgaraM, etal.C-reaetive proteinasa predictor of improvement alldre admission in heart failure[J].EurJHeartFail 2002,4:331-336.
[27]VanhouRePM.Endothelium dependent hyperpolarization beyond nitricoxide and eyelieGMP[J].Circulmion,1995:93(11):3337-3349.
[28]MattusehF,DufaUXB,HeineO,etal.Reduction of the plasma eoneentration of C-reactive protein following nine months of endurance training[J].IntJ SportsMed,2000:21(1):21-24.
[29]刘福明,赵志英,唐蜀华.甲状腺激素与充血性心力衰竭相关性研究进展[J].中国临床医学,2006,13(3)
[30]MadsenB, KellerN.ChristiansenE.Prognostie Value of plasma Eateeholamine Plasmaren activity, and plasma atrial natriuretic peptide at rest and during exercise in congestive heart failure:comparison with clinical evaluation, ejection fraction and exercise capacity[J].JCardFail,1995,1:207-216.
[31]AN KER SD,DOEHNER W,RAUCHHAUS M,etal.Uric acid and survival in chronic heart failure:validation and application in metabolic,functional, and hemodynamic staging[J].CirCUlation,2003,107:1991-1997.
[32]李彬,黄艳霞,廖玉华等.慢性心力衰竭患者血尿酸与细胞因子变化的相关性研究[J].实用医学杂志,2003,19(8)：858-859.
[33]CEN GEL A,TURKOGLU S,TURFAN M,etal.Serum uric acid levels as a predictor of in-hospital death in patients h0Spitalized for compensated heart failure[J].Acta Cardiol,2005,60:489-492.
[34]GROOTE P D,MOUQUET F,LAMBL IN N,etal.Serum uric acid is a powerful predictor of survival in paltient s with stable chronic heart failure receiving beta-blocker therapy[J].Circulation,2007,116:650-650.
[35]Muscari A,Bozzoli C,Puddu GM,et al.Association of serum C3 levels with the risk of myocardial infarction[J].Am J Med,1995;98(4):357-364
[36]Muscari A,Massarelli G,Bastagli L,et al.Relationship between serum C3 levels and traditional risk factors for myocardial infarction[J].Acta Crdrdiol,1998;53(6):345-354.
[37]Yudkin JS.Relationlship of serum C3 complement with insulin resistanceand coronary heart disease-cause,consequence or common antecedent?Eur Heart J 2000;21(13):1036-1039
[38]Muscari A,Massarelli G,Bastagli L,et al.Relationship of serum C3 to fasting insulin,risk factors and previous ischaelnic events in middle-aged men[J].Eur Heart J 2000,21(13):1081-1090.
[39]陈灏珠.实用内科学[M].第11版.北京：人民卫生出版社,2001,1239-1241.
[40]Kim DH,Kim GC,Kim SH,et al.The relationship between the left atrial volume and the maximum P-wave and P—wave dispersion in patjentswith congestive heart failure[J].Yonsei Med J.2007,48(5):810-817.
[41]Maekawa Y,Anzai T,Yoshikawa T,et al. Prognostic significance of peripheral monocytosis after reperfused acute myocardial infarction:Apossible role for left ventricular remodeling[J].J Am Coll cardiol.2002.39(2):241-246.
[42]JOH NIA,McMURRAY J V.WH ITMORE J,etal.Anemia and its relatioilship to clinical outcome in heart failure[J]. Circulation,2004,10:149-154.
[43]AlAH MAD A, RAND W M, MANJUNATH G, etal. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction[J].J Am Coll Cardio 1,2003,38:955-962.
[44]Curtis JP, Sokol SI, Wang Y, et al. The association of left ventricular ejection fraction, mortality, and cause of death in stable outpatients with heart failure[J]. J Am Coll Cardiol,2003,42(4):736-742.
[45]Cohn JN. Structure basis for heart failure:ventricular remodeling and its pharmacological inhibition[J]. Circulation,1995,91(10):2504-2507.
[46]孙伯青.益气活血法治疗充血性心力衰竭的临床研究[J].中国中西医结合急救杂志,2006,13(1)：44-46.
[47]吴时达,吴桐,吴昌碧,等.温阳健心灵口服液治疗收缩功能不全性心力衰竭的临床研究[J].中国中西医结合急救杂志,2001,8(2)：223.
[48]李媛,冠心病慢性心功能不全患者心脏舒缩功能与中医证候相关性研究[D].北京：北京中医药大学,2009：67-82.
[49]Fleiss LJ, Levin B, Paik MC. Statistical Methods for Rates and Pro portions.3rd ed, John Wiley & Sons, Inc., NJ, USA,2003.
[50]李文林,赵国平.数据挖掘技术及其在中医药领域的应用[J].中华医学图书情报杂志,2004,13(6)：4-6.
[1]HORNING MG, MURAKAM IS, HORNING EC. Analyses of phospholipids, ceramides, and cerebrosides by gas chromatography and gas chromatography mass spectrometry[J]. Am J Clin Nutr,1971,24(9):1086-1096.
[2]陈灏珠.内科学[M].北京：人民卫生出版社.1995：263-264.
[3]Peiyuan Yin, Patamu Mohemaiti, Jing Chen, et al. Serum metabolic profiling of Abnormal Savda by liquid chromatography/mass spectrometry[J]. J Chromatography B,2008(5):43.
[4]冒海蕾,徐晏,王斌,等.正交信号校正在正常人血清1H-NMR谱的代谢组分析中的滤噪作用评价[J].化学学报,2007,65(2)：152-158.
[5]廖沛球,张晓字,魏来等.基于NMR的代谢组学方法对硝酸钕急性生物效应的研究[J].分析化学,2008,36(4)：426-432.
[6]Gheorgiade M, Bonow RO. Coronary artery disease and chronic heart failure[J]. Circulation,1998;97:282-289.
[7]Nicholson J K,Lindon J C,Holmes E.'Metabonomics' understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J].Xenobiotica,1999,29(11):1181-1189.
[8]Brindle J T, Antti H, Homes E, Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using 1H NMR based metabonomics[J]. Nat Med,2002, 8(12):1439-1444.
[9]Beckwith-Hall BM,Brindle JT,Barton RH,et al.Application of orthogonal signal correction to minimise the effects of physical and biological variation in high resolution 1H NMR spectra of biofluids[J].Analyst,2002,127(10):1283-1288.
[10]Gavaghan CL,Wilson ID,Nicholson JK.Physiological variation in metabolic phenotyping and functional genomic studies:use of orthogonal signal correction and PLS-DA[J].FEBS Lett,2002,530(1-3):191-196.
[11]Kochhar S,Jacobs DM,Ramadan Z,et al.Probing gender-specific metabolism differences in humans by nuclear magnetic resonance-based metabonomics[J].Anal Biochem,2006,352(2): 274-281.
[12]Stella C,Beckwith-Hall B,Cloarec O,et al.Susceptibility of human metabolic phenotypes to dietary modulation[J].J ProteomeRes,2006,5(10):2780-8.
[13]王勇,李春,郭淑贞等.基于CPMG序列慢性心肌缺血血瘀证血清代谢组学分析[J].北京中医药大学学报,2011,34(12),819-822.
[14]刘舒.肝郁证大鼠血清代谢组学的研究[D].广州：广州中医药大学,2009：58-87.
[15]Zimmerli LU, Schiffer E, Zurbig P,et al. Urinary proteomics biomarkers in coronary artery disease[J]. Mol Cell Proteomics,2008;7:290-298.
[16]李宝成,张怡,熊正英.补充酪氨酸对运动能力影响的可能机制[J].北京体育大学学报.2007,30(1)：68.
[17]周军利,黄跃生,党永明,等.甘氨酸对缺血缺氧心肌细胞能量代谢的影响.[J].现代生物医学进展,2008,8(6)：1093-1095
[18]Heys SD, Ashkanani F.Glutamine[J].BrJSurg,1999,86(3):289-290.
[19]蒋小华,李宁,朱维明.肠内免疫营养对手术创伤后机体免疫炎症反应及预后的影响[J].中国实用外科杂志,2004,24(1)：43.
[20]VanderHulst RR,Von Meyenfeldt MF, DeutzNE, etal. Glutamine extraction by the gut is reduced in depleted[corrected]Patients with gastrointestinal cancer[J].Ann Surg.1997;225(1):112-121.
[21]李康,刘蔚,孙福成等.不同内生肌配清除率对冠心病患者预后的影响[J].中国全科医学,2008,11(6)：936.
[22]MA Mamas, W B Dunn, D Broadhurst, etal. Partial reconstruction of myocardial metabolic pathways following analysis of peripheral serum using metabolomics in early cardiac ischemia.[J]. Heart,2010,96(3):13.
[23]巩菊芳,邵邻相,郑孝华,等.大豆磷脂对红细胞膜脂类成分的影响[J].营养学报,2004,26(3)：180-183.
[24]邵邻相.大豆磷脂对小鼠学习记忆及脑内SOD和脂褐素含量的影响[J].浙江师范大学学报(自然科学版),2003,26(3)：275-276.
[25]何新霞,胡燕月,金晓玲.大豆磷脂对大鼠实验性高脂血症的预防[J].浙江师范大学学报(自然科学版),2001,24(2)：191-193.
[26]肖颖,王军波,梁学军,等.富含单不饱和脂肪酸的坚果对高脂血症患者血脂水平的影响[J].中国公共卫生,2002,18(8)：931-934.
[27]YuanJ.M, etal.Fish and shellfish consumption in relation to death from Myocardial infarction among men in shanghai, China[J]. AmJEPidemiol,2001,154:809-816.
[28]BrielM, Ferreira-Gonzalez I, YouJJ, etal.Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality:systematic review and meta-regression analysis[J].BMJ.2009,16;338:b92.
[29]BaranovaAV.AdiPokine genetics:unbalanced Protein secretion by human adipose tissue as a cause of the metabolic syndrome[J].Genetika.2008 Oct;44(10):1338-55.Review
[30]潘明,陈琼.中医体质、病证研究与代谢组学[J]上海中医药杂志,2008,42(6)：53-56.
[31]董飞侠,黄迪,何立,贾伟.Ⅲ期慢性肾病肾阳虚证患者尿液代谢组学特征的研究[J].中华中医药杂志,2008,23(12)：1109-1113.
[32]朱宣宣,王广基,阿基业,等.冠心病中医辨证分型的代谢组学研究[J].中华中医药学刊,2009,27(6)：1267-1269.
[33]Wang Yong, Li Zhongfeng, Chen Jianxin etal. Study of mini-pig serum of coronary heart disease(chronic myocardial ischemia)with syndrome if blood stasis based on nuclear magnetic resonance metavolomics. Chinese Journal of Analytical Chemistry.2011(8),1274-1278.
[34]华何与,贾饪华,张红栓,等.冠心病心绞痛三种血瘀证的血浆代谢组学研究[J].热带医学杂志,2010,10(3)：258-260,279.
[35]简维雄,袁肇凯,黄献平,等.冠心病心血瘀阻证尿液代谢组学的检测分析[J].中医杂志,2010,51(8)：729-732.
[36]刘卫红,张琪,颜贤忠,等.高脂血症及动脉粥样硬化痰瘀演变的代谢组学研究[J].中医杂志.2008,49(8)：738-741.
[37]Expert Panel on Detection,Evaluation,and Treatment of High Blood Cholesterol in Adults.Executive Summary of The Third Report of The National Cholesterol Education Program(NCEP) Expert Panel on Detection,Evaluation,And Treatment of High Blood Cholesterol In Adults(Adult Treatment Panel III) [J].JAMA,2001,285:2486-2497.
[38]Nobuko H, Dileep S.S. Carnitine and Choline Supplementation with Exercise Alter Carnitine Profiles, Biochemical Markers of Fat Metabolism and Serum Leptin Concentration in Healthy Women.[J].J. Nutr.,2003,133(1):84-89.
[39]Kove E.Wakenell, P.Klasing, K.C.Dietary fish oil or lofrin, a 5-liPoxyenase inhibitor, decrease the growth-suppressing effects of coccidiosis in broilerchicks[J].Poultry sci,1997, 76:1335-1363.
[40]严蓓,阿基业,郝海平等.心血瘀阻组与气阴两虚证心肌缺血大鼠模型的代谢组学表征与辨识[J].中国科学C辑：生命科学,2008,38(12)：1143-1151.
[41]马文军；张涛.运动减肥与肉碱的关系[J].武汉体育学院学报,2003,36(5)：52-53.
[42]陈冬梅.虚寒证的证候规律及其代谢组学的研究[D].河北医科大学,2008：35-39.
[43]吕爱平,李德新,崔家鹏,等.脾肾阳虚模型大鼠肝细胞线粒体磷脂组分变化的比较研究[J].中医药学刊.2003,23(1)：78,83.
[44]Nicholson J K, Holmes E, Lindon J C, et al. The challenges of modeling mammalian biocomplexity[J]. Nat Biotechnol,2004,22(10):1268.