【作者】 吴华慧；

【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：通过观察养心汤对室性早搏(气血亏虚型)患者的临床疗效及对室性早搏患者的血清miRNA-1和尿代谢组学的影响,初步探讨室性早搏患者的发病机制及探寻其相关代谢组学标志物。方法：本研究将入选的100例室性早搏患者随机分为治疗组和对照组,在治疗原发疾病的基础上,对照组常规服用慢心律150mg,日3次口服；治疗组口服慢心律150mg,日3次口服,并同时给予养心汤150ml,日2次口服,治疗四周为一疗程。观察治疗前后的中医症候、24h室性早搏数QT离散度的变化。从上述患者中随机抽取治疗组和对照组各10例,测定治疗前后的血清miRNA-1。另从研究观察患者中随机抽取治疗组和对照组各10例,另选取健康志愿者10例,采用UPLC-TOF/MS代谢组学技术观察室性早搏患者用药前后尿代谢物成分的变化,采用主成分分析(PCA)、偏最小二乘判别分析(PLS-DA)和正交校正的偏最小二乘判别分析(OPLS-DA),寻找室性早搏患者的相关代谢组学标志物。结果：1、治疗组临床症状改善总有效率达89.79%,对照组有效率为60.42%,与对照组比较有统计学意义(P<0.05)。2、治疗组室性早搏控制总有效率达79.59%,对照组室性早搏治疗有效率达62.5%,与对照组比较疗效显著(P<0.05)。3、治疗组在治疗后中医症状积分明显下降(P<0.01),对照组在治疗后中医症状积分亦有下降趋势与疗前比较P<0.05,与对照组比较,治疗组疗后中医症状积分下降更明显(P<0.01)。4、治疗组和对照组在治疗后患者的QT离散度均有明显下降,有统计学意义,治疗组在治疗后QT离散度下降较对照组更为显著,两者比较有统计学意义(P<0.05)。5、治疗组和对照组在治疗前miRNA-1水平表达较高,作治疗后均有不同程度的下降(P<0.05)。治疗组疗后与对照组疗后比较miRNA-1下降更明显(P<0.05)。6、室性早搏患者的尿中羧酸酯、酰基辅酶A脱氢酶、异戊酸、酰基肉碱比正常组有明显降低；经治疗后,治疗组和对照组均有一定上升,治疗组在治疗后上调的更明显。结论：1、养心汤能改善气血亏虚型室性早搏患者的临床症状。2、养心汤能减少气血亏虚型室性早搏患者的室性早搏次数,缩短室性早搏患者的QT离散度。3、养心汤能降低室性早搏患者血清中miRNA-1的水平,并对气血亏虚型室性早搏患者尿中的羧酸酯、酰基辅酶A脱氢酶、异戊酸、酰基肉碱代谢产物具有调节作用。更多还原

【Abstract】 Objective:Through investigating the clinical efficancy of Yang Xin Tang to the patients with ventricular premature beats in Syndrome of asthenia of Qi and blood and effects to serum miRNA-1and urine metabolomics of patients with ventricular premature beats,preliminary study the pathogenesis of patients with ventricular premature beats and explore its metabolomics markers.Methods:In this study,100patients with ventricular premature beats were randomly divided into treatment and control groups,and four weeks of a course of treatment,observing TCM symptoms before and after treatment,24h ventricular premature beats, and QT dispersion changes. The patients from the first part were randomly selected treatment group and control group10cases,determinating serum miRNA-1before and after treatment. The patients from the first part randomly selected treatment group and control group10cases, and the other10cases were selected from healthy volunteers,observing ventricular premature contraction in patients with medication changes in the composition by using urinary metabolites before and after UPLC-TOF/MS metabolomics techniques, and looking for ventricular premature beats in patients with metabolic group markers by the use of principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal correction partial least squares discriminant analysis (OPLS-DA).Results:1. the treatment group to improve the total effective rate was89.79%, the control group was60.42%, and it was statistically significant compared with control group(P<0.05).2.the treatment group, ventricular premature beats control the total effective rate was79.59%,in the control group of ventricular premature beats treatment rate of62.5%compared with the control group a significant effect (P<0.05).3.the treatment group after treatment, TCM syndrome score decreased significantly (P<0.01), the control group after treatment, TCM syndromes integral is also a downward trend and treatment, P<0.05, treatment and control groups after the treatment of TCM symptom scores decreased more significantly (P<0.01).4.treatment and control groups in the treatment of patients with QT dispersion have decreased significantly, with statistical significance, the treatment group after treatment, QT dispersion decreased compared with the control group is more significant, both statistically significant (P<0.05).5. treatment and control groups before treatment miRNA-1level higher expression, in varying degrees after treatment decreased (P<0.05). The treatment group after treatment of miRNA-1decreased more significantly compared with the control group after treatment(P<0.05).6.Urine metabolomics studies have shown that:the tryptophan in the urine of patients with ventricular premature beats, carboxylic esters, acyl-coenzyme A dehydrogenase, isovaleric acid was significantly reduced than the normal group.after treatment, the treatment group was increased more obviously than control group.Conclusion:1.Yang Xin Tang can significantly improve clinical sympto-ms in patients with ventricular premature beats.2.Yang Xin Tang can significantly reduce the incidence of premature ventricular beats and shorten the QT dispersion in patients with ventricular premature beats.3.Yang Xin Tang can significantly reduce the level of serum of miRNA-1of patients with ventricular premature beats.5. Yang Xin Tang can interfere with some urine metabolomics markers in patients with ventricular premature beats.更多还原