UPLC-Q-TOF-MS/MS Metabolomics Analysis of the Effect of Acupuncture on Changes in Plasma Metabolites in Patients with Depression
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摘要:
目的 运用高效液相色谱-飞行时间质谱联用(UPLC-Q-TOF-MS/MS)技术研究针刺治疗抑郁症的潜在生物标志物, 探究针刺抗抑郁的潜在代谢调节机制。 方法 选取2017年10月至2018年6月南京脑科医院的抑郁症患者25例, 随机分为针刺药物组13例和药物组12例(脱落4例), 药物组予SSRIs口服治疗, 针刺药物组在药物组治疗基础上加予耳内皮刺治疗。收集治疗前后2组患者血浆样品, 运用UPLC-Q-TOF/MS检测治疗前后2组患者的血浆代谢产物, 比较2组治疗前后代谢物的差异。 结果 针刺药物组筛选出16个潜在生物标记物, 推测针刺药物组通过调节苯丙氨酸代谢、组氨酸代谢、酮体的合成与降解、赖氨酸降解4条代谢途径改善抑郁症患者的异常状态。药物组筛选出9个潜在生物标记物, 推测药物组通过调节亚油酸代谢、咖啡因代谢、牛磺酸和亚牛磺酸的代谢、精氨酸和脯氨酸代谢4条代谢途径发挥治疗作用。 结论 对抑郁症患者代谢物的调控可能是针刺发挥抗抑郁作用的内在机制。 -
关键词:
- 针刺 /
- 抑郁症 /
- 代谢组学 /
- UPLC-Q-TOF-MS/MS
Abstract:OBJECTIVE Using UPLC-Q-TOF-MS/MS to study the potential biomarkers of acupuncture in the treatment of depression, and to explore the potential metabolic regulatory mechanism of acupuncture treatment for depression. METHODS 25 depression patients from Nanjing brain hospital from October 2017 to June 2018 were selected and randomly divided into 13 cases in acupuncture drug group and 12 cases in drug group(with 4 cases fell off). The drug group received oral treatment with SSRIs, while the acupuncture drug group received ear endothelial puncture treatment in addition to the treatment of drug group. Plasma samples were collected from the two groups of patients before and after treatment, and UPLC-Q-TOF-MS/MS was used to detect plasma metabolites before and after treatment. The differences in metabolites between the two groups were compared before and after treatment. RESULTS 16 potential biomarkers were screened out in the acupuncture drug group. It is speculated that the acupuncture drug group can improve the abnormal metabolism of patients with depression by regulating phenylalanine metabolism, histidine metabolism, synthesis and degradation of ketone bodies, and lysine degradation. 9 potential biomarkers were screened out in the drug group. It is speculated that the acupuncture drug group improves abnormal metabolism in patients with depression by regulating the four metabolic pathways: phenylalanine metabolism, histidine metabolism, ketone synthesis and degradation, and lysine degradation. CONCLUSION The regulation of metabolites in patients with depression may be the internal mechanism by which acupuncture exerts its antidepressant effect. -
Key words:
- acupuncture /
- depression /
- metabolomics /
- UPLC-Q-TOF-MS/MS
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图 1 正离子模式下各组血浆样本总离子流图(TIC)
注: A.针刺药物组; B.药物组
Figure 1. Total ion chromatogram of plasma samples from each group in positive ion mode
图 2 PCA图及PLS-DA图
注: AB.针刺给药前; ab.针刺给药后; DE.给药前; de.给药后; ①③⑤⑦.PCA图; ②④⑥⑧.PLS-DA图
Figure 2. PCA and PLS-DA scores plot of each group
图 3 PLS-DA置换检验图
注: ①.针刺药物组; ②.药物组; ③.治疗前对比; ④.治疗后对比
Figure 3. Permutation test of PLS-DA model
图 4 针刺药物组显著性差异代谢物层次聚类结果
Figure 4. The hierarchical clustering results of significantly potential metabolites in acupuncture-drug group
图 5 药物组显著性差异代谢物层次聚类结果
Figure 5. The hierarchical clustering results of significantly potential metabolites in drug group
图 6 针刺药物组治疗前后血浆差异代谢通路
注：a1.酮体的合成与降解; b1.赖氨酸降解；c1.苯丙氨酸代谢；d1.组氨酸代谢
Figure 6. Differential metabolic pathways in plasma before and after treatment in acupuncture-drug group
图 7 药物组治疗前后血浆差异代谢通路
注：a.亚油酸代谢; b.咖啡因代谢; c.牛磺酸和牛磺酸的代谢; d.精氨酸和脯氨酸代谢
Figure 7. Plasma differential metabolic pathways before and after treatment in drug group
表 1 2组患者基线资料比较(x±s)
Table 1. Comparison of baseline data between the two groups (x±s)
组别 例数 年龄/岁 HAMD指数 性别 男 女 药物组 8 55.88±9.16 19.92±2.61 3 5 针刺药物组 13 50.15±10.42 20.00±0.82 7 6 
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表 2 各组间PLS-DA模型参数表
Table 2. Evaluation parameter of PLS-DA in each group
组别 Type A N R2X(cum) R2Y(cum) Q2(cum) AB-ab PLS-DA 3 26 0.517 0.966 0.655 DE-de PLS-DA 3 16 0.528 0.993 0.546 AB-DE PLS-DA 3 21 0.364 0.972 0.604 ab-de PLS-DA 3 21 0.426 0.975 0.793
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表 3 针刺药物组抑郁症患者的潜在生物标志物
Table 3. Potential biomarkers of depressed patient in acupuncture-drug group
编号 tR/min VIP m/z 化学式 标志物 HMDB KEGG MS/MS 误差 1 3.59 2.455 21 328.488 3 C22H32O2 二十二碳六烯酸 0002183 C06429 329.323 4 [M+H]+ 0.8 2 7.76 1.793 47 256.424 1 C16H32O2 棕榈酸 0000220 C00249 257.196 5 [M+H]+ -0.2 3 6.01 1.800 03 102.088 6 C4H6O3 乙酰乙酸 0000060 C00164 103.051 5[M+H]+ 0.3 4 6.85 2.379 28 114.102 6 C4H6N2O2 N-甲基乙内酰脲 0003646 C02565 115.052 3[M+H]+ 1.2 5 7.86 1.864 18 136.147 9 C8H8O2 苯乙酸 0000209 C07086 137.045 0[M+H]+ -2.1 6 9.08 1.955 37 184.146 1 C8H8O5 3, 4-二羟基扁桃酸 0001866 C05580 185.128 2[M+H]+ 0.2 7 8.38 1.958 06 180.155 9 C6H12O6 D-葡萄糖 0000122 C00221 181.061 7[M+H]+ 0.4 8 7.10 2.683 21 386.653 5 C27H46O 5α-Cholest-8-en-3β-ol 0006841 C03845 387.192 5[M+H]+ -0.6 9 0.53 1.917 67 117.146 3 C5H11NO2 L-缬氨酸 0000883 C00183 118.088 1[M+H]+ 2.4 10 4.50 2.328 25 138.122 0 C7H6O3 3-羟基苯甲酸 0002466 C00587 139.039 7[M+H]+ -0.9 11 3.41 2.241 16 146.187 6 C6H14N2O2 L-赖氨酸 0000182 C00047 147.085 5[M+H]+ -3.0 12 3.06 2.139 30 117.146 3 C5H11NO2 N, N, N-三甲基甘氨酸 0015550 C07457 118.088 3[M+H]+ 2.4 13 8.10 2.192 92 155.154 6 C6H9N3O2 L-组氨酸 0000177 C00135 156.133 1[M+H]+ -1.8 14 3.19 2.015 83 164.158 0 C9H8O3 苯丙酮酸 0000205 C00166 165.100 9[M+H]+ 4.0 15 9.98 1.947 90 136.111 5 C5H4N4O 次黄嘌呤 0000157 C00262 137.047 0[M+H]+ 3.7 16 8.28 1.947 68 88.105 1 C4H8O2 异丁酸 0001873 C02632 89.507 6[M+H]+ 1.8
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表 4 药物组抑郁症患者的潜在生物标志物
Table 4. Potential biomarkers of depressed patient in drug group
编号 tR/min VIP m/z 化学式 标志物 HMDB KEGG MS/MS 误差 1 6.02 1.354 90 280.445 5 C18H32O2 亚油酸 0000673 C01595 281.139 9[M+H]+ -3.6 2 7.18 1.228 91 180.155 9 C6H12O6 D-果糖 0000660 C02336 181.103 8[M+H]+ 1.0 3 7.16 1.387 17 164.158 0 C9H8O3 4-羟基肉桂酸 0002035 C00811 165.060 3[M+H]+ 3.3 4 7.66 1.415 09 140.031 9 C2H5O5P 乙酰磷酸酯 0001494 C00227 141.116 7[M+H]+ 1.1 5 10.13 1.322 08 129.157 0 C6H11NO2 氨己烯酸 0015212 C07500 130.159 9[M+H]+ 2.8 6 10.09 1.392 56 115.130 5 C5H9NO2 脯氨酸 0000162 C00148 116.105 9[M+H]+ 0.4 7 6.96 1.430 00 180.164 0 C7H8N4O2 对黄嘌呤 0001860 C13747 181.065 4[M+H]+ -0.3 8 6.00 1.463 78 90.077 9 C3H603 甘油醛 0001051 C02154 91.058 9[M+H]+ -2.4 9 8.16 1.587 89 114.099 3 C5H6O3 顺式丙烯酸乙酰酯 0060461 C07091 115.052 3[M+H]+ 0.1
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