基于液相色谱—质谱联用的针刺治疗原发性高血压的血浆代谢全谱分析

发布时间：2018-01-25 12:07

本文关键词： 针刺原发性高血压代谢组学液相色谱-质谱分析　出处：《成都中医药大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的：采用液相色谱-质谱联用(Liquid Chromatography-Mass Spectrometry, LC/MS)技术,研究原发性高血压(Essential Hypertension, EH)患者和健康受试者血浆代谢物的差别,并观察针刺对EH患者血浆代谢物的影响。方法：1.EH患者的血浆代谢全谱分析：采用LC/MS技术,分析EH患者与健康受试者血浆代谢物的差别,获得EH关键代谢物。2.针刺治疗EH的血浆代谢全谱分析：分别采用经穴、非经非穴两种方法针刺治疗EH患者,运用LC/MS代谢组学技术,观察针刺对EH患者血浆代谢物的影响以及组间差异。3.差异代谢物与临床血压相关性分析：采用24h动态血压仪监测患者全天的平均血压,运用Pearson线性相关分析,筛选出与针刺治疗EH疗效相关的代谢物,找到EH的潜在生物标志物。结果：1.EH患者的血浆代谢全谱分析结果利用LC/MS技术能较好区分EH患者与健康受试者的代谢状态。与健康对照组相比,EH患者血浆中差异m/z126.1030(3-甲基组氨酸)、530.2777(甘氨酸)、284.2949(鞘氨醇)等浓度显著上升(P0.05)；差异m/z229.1176(门冬氨酸、亮氨酸、异亮氨酸)等浓度显著下降(P0.05)。2.针刺治疗EH的血浆代谢全谱分析结果(1)经穴治疗EH患者的临床效应优于非经非穴组,并能显著改善EH患者的24小时平均收缩压、24小时平均舒张压、日间平均收缩压和日间平均舒张压；非经非穴针刺治疗EH患者血压降低不明显,无统计学差异(P0.05)。(2)采用LC/MS技术能较好区分EH患者针刺治疗前后以及针刺组间的代谢状态。(3)经穴组患者血浆中差异m/z387.1283(油酸)的浓度在针刺后显著上升；非经非穴组血浆中差异m/z265.1]75(苯丙氨酸)的浓度在针刺后显著下降；与非经非穴组相比,经穴组患者治疗后血浆代谢物中差异m/z450.2977(溶血磷脂酰胆碱LysoPC(14:0))浓度显著上升(P0.05),差异m/z287.2362(花生四烯酸)浓度显著下降(P0.05)。3.差异代谢物与临床血压相关性分析结果(1)受试者基线期血浆代谢物浓度与患者的24小时平均收缩压、24小时平均舒张压进行Pearson线性相关分析结果显示,差异m/z126.1030(3-甲基组氨酸)与24h平均收缩压显著负相关(P0.05),530.2777(甘氨酸)、607.3059(胆酸葡萄糖醛酸)、284.2949(鞘氨醇)与24h平均舒张压显著正相关(P0.05)。(2)EH患者针刺前后血浆代谢物浓度变化值与患者24小时平均收缩压、24小时平均舒张压血压变化值的Pearson线性相关分析结果显示,差异m/z211.1441(脯氨酸)的改变值与24h平均收缩压改变值显著负相关(P0.05),差异m/z263.0896(脂肪酸：3-Carboxy-4-me thyl-5-propyl-2-furanpropionic acid)与24h平均舒张压显著正相关(P0.05),454.3150(脂肪酸：simvastatin hydroxy acid)与24h平均舒张压显著负相关(P0.05)。结论：1.EH患者血浆代谢全谱与健康对照组不同,主要集中在氨基酸代谢、脂代谢方面。2.经穴与非经非穴两种治疗方式对EH患者的血浆代谢物均有一定的调节作用,但调节的代谢物不同,EH患者血浆代谢物与临床血压存在一定相关性。
[Abstract]:Objective: to use liquid Chromatography-Mass spectrometric (LC / MS) technique by liquid chromatography-mass spectrometry (LC-MS). To study the difference of plasma metabolites between patients with essential hypertension (EH) and healthy subjects. To observe the effect of acupuncture on plasma metabolites in EH patients. Methods 1. Total spectrum analysis of plasma metabolism in EH patients. The difference of plasma metabolites between EH patients and healthy subjects was analyzed by LC/MS technique. Obtain essential metabolite of EH .2.The whole spectrum analysis of plasma metabolism in acupuncture treatment of EH: acupuncture at meridian and non-meridian points were used to treat EH patients, and LC/MS metabolomics technique was used to treat EH patients. To observe the effect of acupuncture on plasma metabolites of EH patients and the difference between groups. 3. Analysis of the correlation between different metabolites and clinical blood pressure: 24 hours ambulatory blood pressure instrument was used to monitor the mean blood pressure of the patients all day. Pearson linear correlation analysis was used to screen the metabolites related to the effect of acupuncture on EH. Find potential biomarkers for EH. Results:. 1. The results of plasma metabolic total spectrum analysis of EH patients were compared with those of healthy subjects. 2. LC/MS technique was used to distinguish the metabolic status between EH patients and healthy subjects. The difference in plasma levels between patients with EH was m / z126.1030m- methylhistidine 530.2777 (glycine). 284.2949 (sphingosine) etc. The difference was m / z 229.1176 (aspartate, leucine). The plasma metabolism of EH treated by acupuncture was significantly decreased (P0.05n.2.The results of total spectrum analysis of plasma metabolism of acupuncture) showed that the clinical effect of acupoint therapy on EH patients was better than that of non-acupoints group. The mean systolic blood pressure of 24 hours, the mean systolic blood pressure during day and the average diastolic blood pressure in day were significantly improved in patients with EH. There was no significant decrease in blood pressure in EH patients treated with non-meridian and non-acupoint acupuncture. There was no statistical difference (P 0.05). (2) LC/MS technique was used to distinguish the metabolic state of EH patients before and after acupuncture treatment and between acupuncture groups (P < 0.05). The difference in plasma concentration of m / z 387.1283 (oleic acid) in acupoint group increased significantly after acupuncture. The concentration of phenylalanine in the plasma of non-meridian and non-acupoint group decreased significantly after acupuncture, and the difference of m / z 265.1] 75 (phenylalanine) was observed. Compared with non-meridian non-acupoint group. After treatment, the difference of plasma metabolites in the meridian acupoint group was that the concentration of lysophosphatidylcholine (lysophosphatidylcholine, LysoPC14: 0) increased significantly (P0.05). The difference of m / z _ 287.2362 (arachidonic acid) concentration was significantly decreased (P _ (0.05) n 路3). The correlation between different metabolites and clinical blood pressure was (1). Baseline plasma metabolite concentrations and 24-hour mean systolic blood pressure in subjects. 24 hours mean diastolic blood pressure was analyzed by Pearson linear correlation analysis. The difference between m / z 126.1030 and 3-methylhistidine was negatively correlated with 24 h mean systolic blood pressure (P 0.05) and 530.2777 (glycine). 607.3059 (cholic acid glucuronic acid). 284.2949 (sphingosine) and 24h mean diastolic blood pressure were positively correlated with plasma metabolites concentration before and after acupuncture and 24 hours mean systolic blood pressure. Pearson linear correlation analysis of 24 hour mean diastolic blood pressure (DBP) changes showed. There was a significant negative correlation between the variation of proline and 24 h mean systolic blood pressure (P 0.05). Difference (fatty acid: 3-Carboxy-4-me thyl-5-propyl-2-furanpropionic acid). There was a significant positive correlation with 24 h mean diastolic blood pressure (P 0.05). 454.3150 (fatty acid: simvastatin hydroxy acid) was negatively correlated with 24-hour mean diastolic pressure (P 0.05). Conclusion: 1. The whole spectrum of plasma metabolism in EH patients is different from that in healthy controls. Mainly concentrated in the metabolism of amino acids, lipid metabolism. 2. Both meridian and non-meridian points have a certain regulatory effect on plasma metabolites in EH patients, but the regulated metabolites are different. Plasma metabolites were correlated with clinical blood pressure in EH patients.
【学位授予单位】：成都中医药大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R246.1

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