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基于氢核磁共振和质谱代谢组学研究杜仲降压片与苯磺酸氨氯地平联用对自发性高血压大鼠的协同治疗作用

Synergistic therapeutic effects of Duzhong Jiangya Tablets and amlodipine besylate combination in spontaneously hypertensive rats using H-NMR- and MS-based metabolomics.

作者信息

Li Jingwei, Zhao Min, Jiang Xue, Liu Tingting, Wang Miao, Zhao Chunjie

机构信息

School of Pharmacy, Shenyang, Liaoning Province, China.

School of Life Science and Biopharmaceutics, Shenyang, Liaoning Province, China.

出版信息

Biomed Chromatogr. 2020 Apr;34(4):e4741. doi: 10.1002/bmc.4741. Epub 2020 Jan 21.

Abstract

Duzhong Jiangya Tablet (DJT) composed of Eucommia ulmoides Oliv. and several other traditional Chinese medicines is a Chinese herbal compound, which is clinically used to treat hypertension. The aim of this study was to evaluate the antihypertensive effect of DJT and amlodipine besylate (AB) on the synergistic treatment of spontaneously hypertensive rats (SHRs), and to explore its antihypertensive mechanism. The synergistic therapeutic effect of DJT in combination with AB on SHR was studied using two metabolomics methods based on mass spectrum (MS) and nuclear magnetic resonance. Metabolomics analysis of plasma, urine, liver, and kidney and the combination of orthogonal partial least squares discriminant analysis was performed to expose potential biomarkers. Then, the overall metabolic characteristics and related abnormal metabolic pathways in hypertensive rats were constructed. Blood pressure measurements showed that DJT combined with AB has better effects in treating hypertension than it being alone. A total of 30 biomarkers were identified, indicating that hypertension disrupted the balance of multiple metabolic pathways in the body, and that combined administration restored metabolite levels better than their administration alone. The changes of biomarkers revealed the synergistic therapeutic mechanism of DJT combined with AB, which provided a reference for the combination of Chinese and Western medicines.

摘要

杜仲降压片(DJT)由杜仲等多种中药组成,是一种复方中药制剂,临床用于治疗高血压。本研究旨在评价杜仲降压片与苯磺酸氨氯地平(AB)联合应用对自发性高血压大鼠(SHR)的协同降压作用,并探讨其降压机制。采用基于质谱(MS)和核磁共振的两种代谢组学方法,研究杜仲降压片与AB联合应用对SHR的协同治疗效果。对血浆、尿液、肝脏和肾脏进行代谢组学分析,并结合正交偏最小二乘法判别分析,以揭示潜在的生物标志物。然后,构建高血压大鼠的整体代谢特征和相关异常代谢途径。血压测量结果表明,杜仲降压片与AB联合应用治疗高血压的效果优于单独使用。共鉴定出30种生物标志物,表明高血压破坏了体内多种代谢途径的平衡,联合给药比单独给药能更好地恢复代谢物水平。生物标志物的变化揭示了杜仲降压片与AB联合应用的协同治疗机制,为中西医结合提供了参考。

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