原发性肾病综合征脾肾阳虚证患者血清及尿液代谢组学的研究
发布时间：2018-09-17 15:56
【摘要】：目的:本研究运用代谢组学技术,对健康人群和原发性肾病综合征(PNS)脾肾阳虚证患者的血清、尿液进行核磁共振氢谱(1H-NMR)图谱分析,寻找PNS脾肾阳虚证型潜在的生物标志物;利用代谢组学技术探索PNS脾肾阳虚证型的中医证候物质基础,以期建立PNS脾肾阳虚证型的中医辨证分型的客观化、定量科学表达体系,为中医药诊治PNS提供新的思路与方法。方法:本研究以2014年5月-2015年6月25例就诊于我院明确诊断为原发性肾病综合征并辨证为脾肾阳虚证型患者为研究对象,另以25例健康人(健康人来源为病人家属志愿者)作为正常对照组,收集受试者血清、尿液(晨尿)标本,并记录他们的性别、年龄、血液生化、尿液生化等信息。对血清、尿液样本进行1H-NMR检测,对所得核磁数据分段积分后导入SIMCA-P 13软件多元统计分析。首先采用无监督的主成分(PCA)分析,再采用有监督的正交偏最小二乘法判别(O/PLS-DA)分析,在所得模型参数有效的基础上,根据VIP值和载荷图(S-plot),确认差异代谢产物,得出证候的物质基础,探索PNS脾肾阳虚证型的代谢物变化规律。结果:(1)PNS脾肾阳虚证型组血清、尿液核磁图谱直观分析显示,与正常对照组相比,两组间血清、尿液组成明显不同,且存在统计学差异(P0.05)。(2)根据PNS脾肾阳虚证组与正常对照组血清核磁数据的S-plot和VIP值,分析得出7个内源性代谢物与正常对照组相比具有统计学差异(P0.05),其中脂质,丙酮酸含量升高,而缬氨酸、亮氨酸、N-乙酰糖胺、谷氨酰胺、甘油含量下降(P0.05)。(3)根据PNS脾肾阳虚证组与正常对照组尿液核磁数据的S-plot和VIP值,分析得5个内源性代谢物与正常对照组相比具有统计学差异(P0.05),其中亮氨酸、乳酸、甜菜碱含量升高,而肌酐、马尿酸含量下降(P0.05)。结论:原发性肾病综合征脾肾阳虚证患者血清及尿液核磁代谢图谱与正常对照组相比较有显著差异,在主成份分析基础上能将差异代谢产物分开;从本研究的初步结果可以得出PNS脾肾阳虚证在代谢组学水平上有着特定的代谢轮廓,主要涉及脂质、氨基酸、三羧酸循环等代谢紊乱。但由于本项目未进行PNS脾肾阳虚证与PNS其他证型代谢组学特点的对照研究,故尚无法判断本研究得出的PNS脾肾阳虚证特征性表现中哪些属于PNS的共性因素,哪些属于PNS脾肾阳虚证的特征性表现,有待在今后的实验中进一步完善。
[Abstract]:Objective: to investigate the potential biomarkers of (PNS) spleen and kidney yang deficiency syndrome (PNS) by using metabolic techniques to analyze the serum and urine of healthy people and patients with primary nephrotic syndrome (PNS) with spleen and kidney yang deficiency syndrome (PNS). The substance basis of TCM syndromes of PNS type of spleen and kidney yang deficiency syndrome was explored by using metabolomics technique, in order to establish the objectification and quantitative scientific expression system of TCM syndrome differentiation of PNS type of spleen and kidney yang deficiency syndrome, and to provide a new way of thinking and method for the diagnosis and treatment of PNS by traditional Chinese medicine. Methods: from May 2014 to June 2015, 25 patients with primary nephrotic syndrome and syndrome differentiation of spleen and kidney yang deficiency were studied. In addition, 25 healthy people (healthy people as family volunteers) were taken as normal control group. The samples of serum and urine (morning urine) were collected, and their sex, age, blood biochemistry, urine biochemistry and other information were recorded. The samples of serum and urine were detected by 1H-NMR, and the nuclear magnetic field data were integrated into SIMCA-P 13 software for multivariate statistical analysis. First, unsupervised principal component (PCA) analysis was used, then supervised orthogonal partial least square (O/PLS-DA) discriminant analysis was used. Based on the valid parameters of the model, the differential metabolites were confirmed according to the VIP value and load diagram (S-plot). The material basis of syndromes was obtained and the changes of metabolites in PNS syndrome of deficiency of spleen and kidney yang were explored. Results: (1) compared with the normal control group, the serum and urine composition of PNS group with spleen and kidney yang deficiency syndrome were significantly different. And there was statistical difference (P0.05). (2) according to the S-plot and VIP values of serum nuclear magnetic field data of PNS spleen and kidney yang deficiency syndrome group and normal control group, the results showed that seven endogenous metabolites had statistical difference compared with normal control group (P0.05), in which the content of lipid and pyruvate increased. However, the contents of valine, leucine N-acetylglyamine, glutamine and glycerol decreased (P0.05). (3) according to the S-plot and VIP values of urine nuclear magnetic field data of PNS group with deficiency of spleen and kidney yang and normal control group. The five endogenous metabolites were significantly different from the normal control group (P0.05). The contents of leucine, lactic acid and betaine increased, while the contents of creatinine and hippuric acid decreased (P0.05). Conclusion: compared with the normal control group, the chromatogram of nuclear magnetic metabolism in serum and urine of the patients with primary nephrotic syndrome with deficiency of spleen and kidney yang has significant difference. On the basis of principal component analysis, the differential metabolites can be separated. From the preliminary results of this study, it can be concluded that PNS spleen and kidney yang deficiency syndrome has a specific metabolic profile at the level of metabolism, mainly involving lipid, amino acid, tricarboxylic acid cycle and other metabolic disorders. But because this item did not carry on the PNS spleen and kidney yang deficiency syndrome and the PNS other syndromes metabonomics characteristic comparative research, therefore has not been able to judge which of the PNS spleen and kidney yang deficiency syndrome characteristic manifestation which belongs to the PNS common factor. The characteristic manifestation of PNS spleen-kidney yang deficiency syndrome needs to be further improved in future experiments.
【学位授予单位】：山西中医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R277.5
本文编号：2246414
[Abstract]:Objective: to investigate the potential biomarkers of (PNS) spleen and kidney yang deficiency syndrome (PNS) by using metabolic techniques to analyze the serum and urine of healthy people and patients with primary nephrotic syndrome (PNS) with spleen and kidney yang deficiency syndrome (PNS). The substance basis of TCM syndromes of PNS type of spleen and kidney yang deficiency syndrome was explored by using metabolomics technique, in order to establish the objectification and quantitative scientific expression system of TCM syndrome differentiation of PNS type of spleen and kidney yang deficiency syndrome, and to provide a new way of thinking and method for the diagnosis and treatment of PNS by traditional Chinese medicine. Methods: from May 2014 to June 2015, 25 patients with primary nephrotic syndrome and syndrome differentiation of spleen and kidney yang deficiency were studied. In addition, 25 healthy people (healthy people as family volunteers) were taken as normal control group. The samples of serum and urine (morning urine) were collected, and their sex, age, blood biochemistry, urine biochemistry and other information were recorded. The samples of serum and urine were detected by 1H-NMR, and the nuclear magnetic field data were integrated into SIMCA-P 13 software for multivariate statistical analysis. First, unsupervised principal component (PCA) analysis was used, then supervised orthogonal partial least square (O/PLS-DA) discriminant analysis was used. Based on the valid parameters of the model, the differential metabolites were confirmed according to the VIP value and load diagram (S-plot). The material basis of syndromes was obtained and the changes of metabolites in PNS syndrome of deficiency of spleen and kidney yang were explored. Results: (1) compared with the normal control group, the serum and urine composition of PNS group with spleen and kidney yang deficiency syndrome were significantly different. And there was statistical difference (P0.05). (2) according to the S-plot and VIP values of serum nuclear magnetic field data of PNS spleen and kidney yang deficiency syndrome group and normal control group, the results showed that seven endogenous metabolites had statistical difference compared with normal control group (P0.05), in which the content of lipid and pyruvate increased. However, the contents of valine, leucine N-acetylglyamine, glutamine and glycerol decreased (P0.05). (3) according to the S-plot and VIP values of urine nuclear magnetic field data of PNS group with deficiency of spleen and kidney yang and normal control group. The five endogenous metabolites were significantly different from the normal control group (P0.05). The contents of leucine, lactic acid and betaine increased, while the contents of creatinine and hippuric acid decreased (P0.05). Conclusion: compared with the normal control group, the chromatogram of nuclear magnetic metabolism in serum and urine of the patients with primary nephrotic syndrome with deficiency of spleen and kidney yang has significant difference. On the basis of principal component analysis, the differential metabolites can be separated. From the preliminary results of this study, it can be concluded that PNS spleen and kidney yang deficiency syndrome has a specific metabolic profile at the level of metabolism, mainly involving lipid, amino acid, tricarboxylic acid cycle and other metabolic disorders. But because this item did not carry on the PNS spleen and kidney yang deficiency syndrome and the PNS other syndromes metabonomics characteristic comparative research, therefore has not been able to judge which of the PNS spleen and kidney yang deficiency syndrome characteristic manifestation which belongs to the PNS common factor. The characteristic manifestation of PNS spleen-kidney yang deficiency syndrome needs to be further improved in future experiments.
【学位授予单位】：山西中医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R277.5
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