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基于高血压肝火上炎证评价罗布麻胶囊疗效及发现代谢机制的高通量代谢组学研究

High-throughput metabolomics for evaluating the efficacy and discovering the metabolic mechanism of Luozhen capsules from the excessive liver-fire syndrome of hypertension.

作者信息

Wang Xi-Jun, Gao Xin, Zhang Ai-Hua, Wu Fang-Fang, Yan Guang-Li, Sun Hui

机构信息

National Engineering Laboratory for the Development of Southwestern Endangered Medicinal Materials, Guangxi Botanical Garden of Medicinal Plant Nanning Guangxi China.

National Chinmedomics Research Center, Sino-America Chinmedomics Technology Collaboration Center, National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine Heping Road 24 Harbin 150040 China

出版信息

RSC Adv. 2019 Oct 9;9(55):32141-32153. doi: 10.1039/c9ra06622e. eCollection 2019 Oct 7.

Abstract

Essential hypertension (EH) is a chronic disease characterized by a variety of causes of elevated systemic arterial pressure, which often causes functional or organic damage to important organs such as the heart, brain, and kidney. Hypertension of excessive liver-fire syndrome is a type of classification for young people with essential hypertension. The disease is slower in its onset and its symptoms are more ambiguous, and thus its pathogenesis is complicated and still unclear. In this study, aconite, dried ginger and cinnamon extracts were combined with l-NAME to establish a model of excessive liver-fire hypertension. Blood pressure (systolic blood pressure), ANGII, NE and 5-HT were used as evaluation indicators to establish the model. Urinary metabolomics based on ultra-high performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was used to characterize the metabolic changes and potential biomarkers in modeled rats. Compared to the treatment group, 32 potential biomarkers were initially identified in the model using multivariate statistical analysis involving 11 metabolic pathways. After oral administration of Luozhen capsules, eight biomarkers that can be adjusted in high, medium and low doses of Luozhen capsules in urine were preliminarily determined, mainly involving two metabolic pathways of amino acid metabolism and lipid metabolism. In conclusion, this study explored the metabolomic changes in rats with hypertension of liver-fire hyperactivity syndrome and the post-dose metabolomics, determined the relevant biomarker groups, and clarified the metabonomic connotation of Luozhen capsules in the treatment of liver-fire excessive type hypertension.

摘要

原发性高血压(EH)是一种以多种原因导致体循环动脉血压升高为特征的慢性疾病,常引起心、脑、肾等重要器官的功能性或器质性损害。肝火亢盛证高血压是原发性高血压青年患者的一种证型分类。该病起病较缓,症状较为隐匿,其发病机制复杂且尚不明确。本研究将附子、干姜和肉桂提取物与L-精氨酸甲酯(L-NAME)联合使用,建立肝火亢盛型高血压模型。以血压(收缩压)、血管紧张素II(ANGII)、去甲肾上腺素(NE)和5-羟色胺(5-HT)作为评价指标来建立模型。基于超高效液相色谱-四极杆飞行时间质谱联用的尿液代谢组学方法用于表征建模大鼠的代谢变化和潜在生物标志物。与治疗组相比,通过涉及11条代谢途径的多元统计分析,在模型中初步鉴定出32种潜在生物标志物。口服罗珍胶囊后,初步确定了尿液中高、中、低剂量罗珍胶囊均可调节的8种生物标志物,主要涉及氨基酸代谢和脂质代谢两条代谢途径。总之,本研究探讨了肝火亢盛证高血压大鼠的代谢组学变化及给药后的代谢组学情况,确定了相关生物标志物组,阐明了罗珍胶囊治疗肝火上炎型高血压的代谢组学内涵。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1728/9072971/10cb2c920213/c9ra06622e-f1.jpg

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