原發(fā)性腎病綜合征脾腎陽虛證患者血清及尿液代謝組學(xué)的研究
發(fā)布時(shí)間：2018-09-17 15:56
【摘要】：目的:本研究運(yùn)用代謝組學(xué)技術(shù),對(duì)健康人群和原發(fā)性腎病綜合征(PNS)脾腎陽虛證患者的血清、尿液進(jìn)行核磁共振氫譜(1H-NMR)圖譜分析,尋找PNS脾腎陽虛證型潛在的生物標(biāo)志物;利用代謝組學(xué)技術(shù)探索PNS脾腎陽虛證型的中醫(yī)證候物質(zhì)基礎(chǔ),以期建立PNS脾腎陽虛證型的中醫(yī)辨證分型的客觀化、定量科學(xué)表達(dá)體系,為中醫(yī)藥診治PNS提供新的思路與方法。方法:本研究以2014年5月-2015年6月25例就診于我院明確診斷為原發(fā)性腎病綜合征并辨證為脾腎陽虛證型患者為研究對(duì)象,另以25例健康人(健康人來源為病人家屬志愿者)作為正常對(duì)照組,收集受試者血清、尿液(晨尿)標(biāo)本,并記錄他們的性別、年齡、血液生化、尿液生化等信息。對(duì)血清、尿液樣本進(jìn)行1H-NMR檢測(cè),對(duì)所得核磁數(shù)據(jù)分段積分后導(dǎo)入SIMCA-P 13軟件多元統(tǒng)計(jì)分析。首先采用無監(jiān)督的主成分(PCA)分析,再采用有監(jiān)督的正交偏最小二乘法判別(O/PLS-DA)分析,在所得模型參數(shù)有效的基礎(chǔ)上,根據(jù)VIP值和載荷圖(S-plot),確認(rèn)差異代謝產(chǎn)物,得出證候的物質(zhì)基礎(chǔ),探索PNS脾腎陽虛證型的代謝物變化規(guī)律。結(jié)果:(1)PNS脾腎陽虛證型組血清、尿液核磁圖譜直觀分析顯示,與正常對(duì)照組相比,兩組間血清、尿液組成明顯不同,且存在統(tǒng)計(jì)學(xué)差異(P0.05)。(2)根據(jù)PNS脾腎陽虛證組與正常對(duì)照組血清核磁數(shù)據(jù)的S-plot和VIP值,分析得出7個(gè)內(nèi)源性代謝物與正常對(duì)照組相比具有統(tǒng)計(jì)學(xué)差異(P0.05),其中脂質(zhì),丙酮酸含量升高,而纈氨酸、亮氨酸、N-乙酰糖胺、谷氨酰胺、甘油含量下降(P0.05)。(3)根據(jù)PNS脾腎陽虛證組與正常對(duì)照組尿液核磁數(shù)據(jù)的S-plot和VIP值,分析得5個(gè)內(nèi)源性代謝物與正常對(duì)照組相比具有統(tǒng)計(jì)學(xué)差異(P0.05),其中亮氨酸、乳酸、甜菜堿含量升高,而肌酐、馬尿酸含量下降(P0.05)。結(jié)論:原發(fā)性腎病綜合征脾腎陽虛證患者血清及尿液核磁代謝圖譜與正常對(duì)照組相比較有顯著差異,在主成份分析基礎(chǔ)上能將差異代謝產(chǎn)物分開;從本研究的初步結(jié)果可以得出PNS脾腎陽虛證在代謝組學(xué)水平上有著特定的代謝輪廓,主要涉及脂質(zhì)、氨基酸、三羧酸循環(huán)等代謝紊亂。但由于本項(xiàng)目未進(jìn)行PNS脾腎陽虛證與PNS其他證型代謝組學(xué)特點(diǎn)的對(duì)照研究,故尚無法判斷本研究得出的PNS脾腎陽虛證特征性表現(xiàn)中哪些屬于PNS的共性因素,哪些屬于PNS脾腎陽虛證的特征性表現(xiàn),有待在今后的實(shí)驗(yàn)中進(jìn)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.
【學(xué)位授予單位】：山西中醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R277.5
本文編號(hào)：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.
【學(xué)位授予單位】：山西中醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R277.5
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