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李琳,钟森杰,李欣春,胡志希.基于代谢组学探讨益气养阴法对高血压心衰的作用机制[J].湖南中医药大学学报,2023,43(3):376-382[点击复制] |
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| 基于代谢组学探讨益气养阴法对高血压心衰的作用机制 |
| 李琳,钟森杰,李欣春,胡志希 |
| (湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 采用高通量代谢组学技术和生物信息学方法探讨益气养阴法对高血压心衰的作用机制，构建代谢调控网络。方法 采用Dahl盐敏感大鼠给予高盐饮食复制高血压心衰大鼠模型，同时采用益气养阴法代表方参麦注射液干预模型，采用气相色谱-质谱联用仪（gas chromatography-mass spectrometer, GC-MS）检测对照（control, CON）组，模型（hypertensive heart failure, H-HF）组，参麦注射液（Shenmai Injection, SMI）组3组大鼠心肌组织代谢产物，每组6只，通过对不同组之间代谢产物含量的变化进行主成分分析，偏最小二乘法分析，筛选高血压心衰生物标志物，使用MetaboAnalyst在线数据库进行代谢通路分析并构建代谢网络。结果 与CON组比较，H-HF组大鼠血清N末端脑钠肽前体(N-terminal-pro-brain-natriuretic-peptide, NT-pro BNP)、血管紧张素Ⅱ(angiotensin Ⅱ, Ang Ⅱ)、内皮素-1(endothelin-1, ET-1)浓度显著升高(P<0.01)，超声心动图左室射血分数（left ventricular ejection fraction, LVEF）、左室短轴缩短率（left ventricular fractional shortening, LVFS）显著下降(P<0.05)，SMI治疗后，血清NT-pro BNP、Ang Ⅱ、ET-1浓度明显下降，超声心动图LVFS值显著上升(P<0.05)，LVEF呈上升趋势，说明参麦注射液可有效改善大鼠心功能。代谢组学检测中，与CON组比较，H-HF组心肌组织中有16种代谢物水平出现明显变化，可能为该模型的生物标志物。SMI治疗后，9种代谢产物显著回调，7种代谢产物表现出调控趋势。代谢通路分析显示，SMI影响最大的通路为精氨酸和脯氨酸代谢（P<0.05）。结论 H-HF组心肌组织代谢组学出现变化，益气养阴法可显著改善高血压心衰大鼠心肌代谢物紊乱，其治疗心衰的作用机制可能与调节糖、氨基酸、乳酸代谢紊乱，从而改善能量代谢有关。 |
| 关键词: 高血压心衰 代谢组学 参麦注射液 益气养阴法 大鼠 气相色谱-质谱联用仪 |
| DOI：10.3969/j.issn.1674-070X.2023.03.003 |
| 投稿时间：2022-06-05 |
| 基金项目:国家自然科学基金项目（82274412）；广东省重点领域研发项目（2020B1111100001）；湖南省中医药科研项目（B2023045）；长沙市自然科学基金项目（kq2208185）。 |
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| Mechanism of tonifying qi and nourishing yin on hypertensive heart failure based on metabonomics |
| LI Lin,ZHONG Senjie,LI Xinchun,HU Zhixi |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To explore the mechanism of tonifying qi and nourishing yin on hypertensive heart failure by using high-throughput metabolomics technology and bioinformatics methods, and then to build a metabolic regulation network. Methods Dahl salt-sensitive rats were given a high-salt diet to create the hypertensive heart failure rat model, and the intervention model of Shenmai Injection, a representative method of tonifying qi and nourishing yin, was adopted. Gas chromatography-mass spectrometer was used to detect the metabolites in myocardial tissue of three groups, namely control (CON) group, hypertensive heart failure (H-HF) group and Shenmai Injection (SMI) group, with 6 rats in each group. According to the content change of the metabolites in each group, the principal component was analyzed, and biomarkers of hypertensive heart failure were screened with partial least square analysis. Metabolic pathway analysis and metabolic network construction were performed by MetaboAnalyst online database. Results Compared with CON group, serum concentrations of N-terminal-pro-brain-natriuretic-peptide(NT-proBNP), angiotensin Ⅱ(Ang Ⅱ) and endothelin-1, (ET-1) of rats in H-HF group were significantly increased (P<0.01), and echocardiogram left ventricular ejection fraction（LVEF）and left ventricular fractional shortening（LVFS） were significantly decreased (P<0.05). After SMI treatment, the serum concentrations of NT-proBNP, Ang Ⅱ and ET-1 significantly decreased. LVFS value of echocardiography significantly increased (P<0.05), the increasing trend of LVEF indicated that Shenmai Injection can effectively improve the cardiac function of rats. Compared with CON group, there were sixteen metabolites in H-HF group showing significant changes in myocardial tissue of hypertensive heart failure, which may be biomarkers of the model. After SMI treatment, 9 metabolites were significantly reduced, and 7 metabolites showed a trend of regulation. Metabolic pathway analysis showed that arginine and proline metabolism were most affected by SMI. Conclusion Myocardial metabolomics of hypertensive heart failure rat model group showed changes and SMI can significantly improve the level of myocardial metabolites in rats with hypertensive heart failure. The mechanism may be related to the regulation of metabolism disorder of glucose metabolism, amino acid and lactic acid, thus improving energy metabolism. |
| Key words: hypertensive heart failure metabonomics Shenmai Injection tonifying qi and nourishing yin rats gas chromatography-mass spectrometer |
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