【作者】 于夕雯；

【导师】 周亚滨；

【作者基本信息】 黑龙江中医药大学 ， 中医内科学， 2012， 博士

【摘要】 目的：通过观察养心汤干预不稳定型心绞痛患者的临床疗效以及对肿瘤坏死因子-α、血浆代谢组学的影响,从而探讨其可能的作用机制,为临床应用提供理论依据。方法：将120例患者随机分成观察组和对照组,对照组给予常规治疗,观察组在常规治疗的基础上加用养心汤,用药疗程4周。观察治疗后的中医症状,心绞痛症状、心电图改善、硝酸甘油停减率变化；在两组临床观察患者中,各随机选取10例,采用聚合酶链反应法观察治疗前后患者血浆中的肿瘤坏死因子-a的变化；在两组临床观察的患者中各随机选取10例及健康志愿者5例,采用液质联用技术观察不稳定型心绞痛患者治疗后血浆代谢物成分的变化,并采用主成分分析、偏最小二乘判别法进行分析观察其代谢组学潜在的生物标志物。结果：1.心绞痛症状积分：观察组总有效率82.76%,对照组为73.68%,两组比较差异具有显著性意义(P<0.05)中医症状积分：观察组总有效率为82.76%,对照组总有效率为68.42%,两组比较差异具有显著性意义(P<0.05)；心电图改善：治疗组总有效率为72.41%,对照组为68.42%两组比较差异无显著性意义(P>0.05)；硝酸甘油停减率：观察组总有效率为79.31%,对照组总有效率为66.67%,两组比较差异具有显著性意义(P<0.05)；两组安全性指标治疗前后无明显差异。2.观察组疗前与对照组疗前肿瘤坏死因子-α比较无显著性差异(P>0.05)；观察组疗后比疗前与对照组疗后比疗前表达水平降低,差异具有显著性意义(P<0.01)。观察组疗后与对照组疗后比较差异具有显著性意义(P<0.05)；3.经养心汤干预的观察组共调节了23个潜在生物标志物,对照组共调节了14个潜在生物标志物,其中有10个潜在生物标志物是观察组和对照组共同调节的。并发现四种物质：前列腺素、甘氨胆酸、色氨酸、石胆酸。治疗前两组比较,生物标志物差异无显著性意义,但与正常组比较具有显著性差异,治疗后两组患者生物标志物明显下调,其中观察组与正常组比较无显著差异,但与对照组比较差异具有显著性意义。结论：1.养心汤可以改善冠心病不稳定型心绞痛患者的中医症状、心绞痛症状及硝酸甘油停减率。2.养心汤可以降低冠心病不稳定型心绞痛患者血浆中肿瘤坏死因子-a的表达。3.①不稳定型心绞痛患者的血浆中的潜在标志物可能为：前列腺素、甘氨胆酸、色氨酸、石胆酸。②养心汤可以改变不稳定型心绞痛患者血浆中潜在标志物的含量。更多还原

【Abstract】 Objective:To observe the clinical efficacy of Yang Xin Tang treatment of unstable angina and to investigate the changes in patients with unstable angina before and after treatment plasma metabolomics.Methods:The clinical trials section:from Changchun University of Traditional Chinese Medicine outpatient selection, completion of clinical trials in patients with a total of115cases, the control group of57cases,58cases of observation group. The former Western standardized treatment observation group was added on the basis of Yang Xin Tang, observed before and after treatment of angina syndrome score, TCM syndrome score, the ECG effects of nitroglycerin stop rates of lipid four and TNF-α endpoint changes and safety items (blood, ALT, and AST, and Cr, BUN,,) changes. Experimental study of parts:selected unstable angina patients and healthy volunteers,10cases of patients with angina medication plasma using LC-MS technique to observe the change in composition of its metabolites using principal component analysis and partial least squares analysis, we found the the metabolomics potential biomarkers. InstabilityResults:1angina symptoms after treatment of the observation group points to improve the overall efficiency of79.31%,73.68%in the control group; observation group points to improve the TCM symptoms was82.76%,68.42%in the control group; in the treatment group improvement of the ECG total effective rate was72.41%and68.42%in the control group; Observer Group of nitroglycerin stop reduction rate of79.31%and66.67%in the control group; two sets of blood lipids after treatment showed some improvements, but the comparative treatment of the observation group than the control group improved significantly P<0.05; two sets of security indicators significant difference before and after treatment. Observed Yang Xin Tang for the instability of angina pectoris tumor necrosis factor, and experimental results show that:observation group after treatment than before treatment, after treatment with the control group before treatment TFF1mRNA expression level, the difference was more significant (P<0.01); observation group after treatment, after treatment with the control group was significant difference (P<0.05); observation group therapy before treatment with the control group the difference was not significant (P>0.05). According to the same screening methods and principles, the tested drugs regulate23potential biomarkers control drugs regulate14potential biomarkers, of which there are10potential biomarkers for the test drug and control drug co-regulated. Common markers:prostaglandin Glycocholic, tryptophan, lithocholic acid. These two groups of patients before treatment, no significant differences in biomarkers, a significant difference compared with normal group. After treatment, biomarkers significant difference, plus Yang Xin Tang observed with the control group, no significant differences, indicating that a correction by Yang Xin Tang treatment after the plasma potential markers.ConclusionYang Xin Tang can significantly improve the TCM symptoms of coronary heart disease in patients with unstable angina, symptoms of angina and nitroglycerin to stop the reduction rate.Yang Xin Tang can significantly reduce the level of tumor necrosis factor in coronary heart disease patients with unstable angina serum, indicating that Yang Xin Tang treatment of unstable angina may be related to the control of the secretion of inflammatory factors.May be potential markers in the3(1) the instability of the plasma of patients with angina pectoris:prostaglandin Glycocholic, tryptophan, and lithocholic acid.(2)Yang Xin Tang can change some of the potential markers in the plasma of patients with unstable angina, and affect the metabolic pathway.更多还原