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养心汤干预不稳定型心绞痛患者的临床研究及代谢组学影响

Clinical Research and Metabolomics on Yang Xin Tang Traditional Chinese Medicine Interventions in Patients with Unstable Angina

【作者】 于晓红

【导师】 周亚滨;

【作者基本信息】 黑龙江中医药大学 , 中医内科学, 2011, 博士

【摘要】 目的:通过观察养心汤对“气虚血少,血液运行无力,心神失养”为病机的不稳定型心绞痛患者的症状、舌象、生活质量的影响,评价其临床疗效;通过观察养心汤对不稳定型心绞痛患者血浆代谢组学的影响,初步探寻不稳定型心绞痛的相关代谢组学标志物。方法:将120例患者随机分为试验组和对照组,试验组在常规治疗基础上加服养心汤,对照组给予常规治疗,疗程4周。观察治疗前后的中医症候、心绞痛症状、心电图、硝酸甘油停减率、舌象、生活质量的变化。选取健康志愿者、不稳定型心绞痛患者各10例,采用液质联用技术观察不稳定型心绞痛患者服药前后血浆代谢物成分的变化,采用主成分分析、偏最小二乘判别法进行分析,寻找不稳定型心绞痛的相关代谢组学标志物。结果:1、心绞痛症状总有效率:试验组94.33%、对照组92%两组比较差异无统计学意义(P>0.05);2、中医症候总有效率:试验组98.11%、对照组94%两组比较差异无统计学意义(P>0.05);3、心电图总有效率:试验组69.81%、对照组64%,两组差异有统计学意义(P<0.05);4、硝酸甘油停减率:试验组62.26%、对照组50%,两组比较差异有统计学意义(P<0.01);5、西雅图心绞痛量表积分:在AS这一维度两组比较差异有统计学意义(P<0.05);6、舌质颜色、舌苔厚度和性质、舌体胖瘦的分布:两组比较差异有统计学意义(P<0.05);7舌色(R/B/G色通量)统计:两组比较差异有统计学意义(P<0.05)。8、D、M、G三组间进行的PCA分析结果:三组样本全部集中分布于得分图的椭圆形(95%置信区内)的4个区域,M组内8、9、10号样品相对离散偏向D组,三组组间基本能分开,M(用药前)组与G(用药后)组间基本能分开。9D组与M组间代谢终产物比较:不稳定型心绞痛组代谢产物中神经酰胺、甘氨胆酸、别胆酸、石胆酸、白三烯B4有明显升高。结论:1、养心汤能明显改善不稳定型心绞痛患者心电图、硝酸甘油停减率。2、养心汤能明显改善不稳定型心绞痛患者心绞痛稳定程度。3、养心汤能明显改善不稳定型心绞痛患者舌质颜色、舌苔厚度和性质、舌体胖瘦的分布情况;但在色分量方法分析上未得到证实。4、神经酰胺、甘氨胆酸、别胆酸、石胆酸、白三烯B4可能是UA代谢组学标志物。5、养心汤对不稳定型心绞痛患者血浆中的某些代谢产物或代谢通路有影响。

【Abstract】 Objective:Clinical study by Yang Xin Tang on the "little blood deficiency, blood running weakness, venae stasis, mind dystrophy" as the pathogenesis of unstable angina (unstable angina pectoris, UA) patients the efficacy and mechanism For Integrative Medicine to develop a comprehensive treatment program UA provide an objective basis. Yang Xin Tang observed UA patients on the impact of metabolomics to explore its possible mechanism of action, the objective for the UA desertification syndromes explored.Methods:A randomized, controlled method 103 patients were divided into experimental group (Yang Xin Tang plus conventional therapy), the control group (conventional therapy), continuous observation for 28 days, on TCM syndrome, angina symptoms, electrocardiogram, Reduced rate of nitroglycerin stop, tongue, quality of life, and follow-up statistics on the changes.The use of liquid chromatography-mass spectrometry technique in 10 healthy volunteers,10 patients with UA were detected in plasma before and after medication, the use of partial least squares discriminant analysis method to observe the UA patients before and after medication changes in composition of plasma metabolites, Metabolomics perspective from Yang Xin Tang on the impact of UA patients, and in the healthy group and disease groups looking for metabolomics markers.Results:1 total effective rate of angina pectoris study group 94.33%,92% of the control group no significant difference between the two groups (P> 0.05).2 TCM symptoms test group the total effective 98.11%,94% of the control group no significant difference between the two groups (P> 0.05).3 ECG test group the total effective rate 69.81%,64% of the control group the difference was statistically significant (P<0.05).4 nitroglycerin stopped by 62.26% rate of the experimental group and control group 50% of the difference was statistically significant (P<0.01).5 Seattle Angina Questionnaire integral dimension in AS the difference between two groups was statistically significant (P<0.05).6, tongue, tongue coating properties, the tongue (tongue questionnaire) statistical difference was statistically significant (P<0.05).7 tongue color (R/B/G color flux) Statistical difference was statistically significant (P<0.05).8D, M, G among the three groups of PCA analysis showed that all three groups of samples concentrated on the score plot of the oval (95% confidence region) of the four regions, M samples of the group There are some differences, showing the relative dispersion of sample bias 8,9,10D, three basic groups can be separated; M (before treatment) group and G (after treatment) can be separated between the two groups basic; 9 D group M group compared metabolic end products found:disease group than in the healthy group elevated metabolites ceramide, Glycocholic acid, not acid, lithocholic acid, leukotriene B4 and so on.Conclusion:1 test group and control group UA group could significantly improve symptoms in patients with Chinese medicine, symptoms of angina, ECG, nitroglycerin stopped by rate. In ECG, the rate of nitroglycerin test group stopped by the degree of improvement than the control group.2 experimental groups and control group could significantly improve the quality of life of patients UA, in Seattle Angina Questionnaire angina stability (AS) the dimension of the experimental group than the control group improvement.3 This study Tongue scale by the experimental group and control group that could significantly improve the tongue in patients with UA, in the tongue, tongue, tongue three degree of improvement in the test group than the control group, The study by digital photography analysis of the tongue did not find experimental group and control group of red /green/blue three color components have changed before and after treatment.4 metabonomics:A study by high performance liquid chromatography mass spectrometry observed in healthy controls and disease groups, Yang Xin Tang UA before and after treatment of the disease in patients with different metabolomics profiles,differences in metabolism between the two groups, there are different pathways that can interfere with UA Yang Xin Tang plasma metabolites or metabolic pathways Erzhi metabolic end Product changes.5This study found that patients with UA may exist: typical signs of metabolites of leukotriene B4, Glycocholic acid, do not lithocholic acid, ceramides.

【关键词】 养心汤心绞痛不稳定型代谢组学
【Key words】 Traditional Chinese medicineAnginaUnstableMetabonomics
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