刘月程, 左振宇, 杜晓蕾, 张会敏, 蒋海强, 苏本正, 周洪雷. 钩藤类方干预高血压肝阳上亢证大鼠的方证相关研究J. 药学学报, 2025, 60(7): 2271-2282. DOI: 10.16438/j.0513-4870.2025-0286
引用本文: 刘月程, 左振宇, 杜晓蕾, 张会敏, 蒋海强, 苏本正, 周洪雷. 钩藤类方干预高血压肝阳上亢证大鼠的方证相关研究J. 药学学报, 2025, 60(7): 2271-2282. DOI: 10.16438/j.0513-4870.2025-0286
LIU Yue-cheng, ZUO Zhen-yu, DU Xiao-lei, ZHANG Hui-min, JIANG Hai-qiang, SU Ben-zheng, ZHOU Hong-lei. Formula-syndrome correlation research on formulas containing Uncaria rhynchophylla intervene hypertension with liver Yang hyperactivity syndrome in ratsJ. Acta Pharmaceutica Sinica, 2025, 60(7): 2271-2282. DOI: 10.16438/j.0513-4870.2025-0286
Citation: LIU Yue-cheng, ZUO Zhen-yu, DU Xiao-lei, ZHANG Hui-min, JIANG Hai-qiang, SU Ben-zheng, ZHOU Hong-lei. Formula-syndrome correlation research on formulas containing Uncaria rhynchophylla intervene hypertension with liver Yang hyperactivity syndrome in ratsJ. Acta Pharmaceutica Sinica, 2025, 60(7): 2271-2282. DOI: 10.16438/j.0513-4870.2025-0286

钩藤类方干预高血压肝阳上亢证大鼠的方证相关研究

Formula-syndrome correlation research on formulas containing Uncaria rhynchophylla intervene hypertension with liver Yang hyperactivity syndrome in rats

  • 摘要: 应用代谢组学技术解读钩藤类方平肝潜阳-肝阳上亢的方证相应, 构建钩藤类方的功效评价方法。以自发性高血压大鼠灌服附子汤制备高血压肝阳上亢证大鼠模型, 分别给予天麻钩藤饮、羚角钩藤汤和清脑降压片, 观测大鼠血压、外观、痛阈、面温、易激惹程度以及24 h饮水量, 使用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱和代谢组学技术分析钩藤类方大鼠血清中差异代谢标志物, 并进行代谢通路分析, 动物实验经山东中医药大学动物伦理委员会批准(伦理号: SDZYY20240304033); 同时根据差异代谢物离子强度变化结合宏观数据判断钩藤类方干预效果, 利用偏最小二乘(partial least squares, PLS) 回归分析筛选出具有显著性差异的代谢标志物。以发现的共同差异代谢物作为肝阳上亢证的核心代谢表型, 整合宏观数据和代谢表型构建钩藤类方的证候功效评价方法。本实验筛选出35个共同差异代谢标志物, 24个差异代谢物在模型组中含量下降, 钩藤类方干预后上升, 11个差异代谢物趋势相反; 代谢通路富集分析表明, 钩藤类方干预通路主要涉及花生四烯酸代谢、不饱和脂肪酸的生物合成、初级胆汁酸生物合成、甘油磷脂代谢; PLS回归分析得到显著性差异代谢物14个, 主要涉及花生四烯酸代谢、不饱和脂肪酸的生物合成、甘油磷脂代谢三条代谢通路; 构建的功效评价方法显示, 天麻钩藤饮干预效果最为明显, 与中医药理论一致。本研究发现了钩藤类方干预肝阳上亢证的共性因子, 揭示了钩藤类方-肝阳上亢方证相关的代谢基础, 构建了钩藤类方的客观化功效评价方法, 为钩藤类方的临床研究提供证据。

     

    Abstract: The study aims to interpret the formula-syndrome correspondence of pacifying liver-subduing Yang and liver Yang hyperactivity from formulas containing Uncaria rhynchophylla based on metabolomics technology, and establish an efficacy evaluation method for these formulas. The rat model of hypertension with liver Yang hyperactivity syndrome was established by intragastrically administering Fuzi Decoction to spontaneously hypertensive rats. Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDZYY20240304033). Tianma Gouteng Decoction, Lingjiao Gouteng Decoction, and Qingnao Jiangya Tablets were respectively administered. The blood pressure, appearance, pain threshold, facial temperature, level of irritability, and 24-hour water intake of the rats were observed. Ultra-high performance liquid chromatography-quadrupole-exactive orbitrap mass spectrometry and metabolomics were used to analyze differential metabolic markers in the serum of rats treated with formulas containing Uncaria rhynchophylla, and metabolic pathway analysis was carried out. Meanwhile the intervention effects of formulas containing Uncaria rhynchophylla were judged according to the changes in the ion intensity of differential metabolites combined with macroscopic data, and partial least squares (PLS) regression analysis was applied to screen significantly differential metabolites. The identified common differential metabolites were regarded as the core metabolic phenotypes of hypertension with liver Yang hyperactivity syndrome. By integrating macroscopic data and metabolic phenotypes, an evaluation method for the syndrome efficacy of Uncaria-based prescriptions was constructed. A total of 35 common differential metabolic markers were identified in this experiment. Among them, 24 differential metabolites decreased in the model group and increased after the intervention of formulas containing Uncaria rhynchophylla, while 11 differential metabolites showed the opposite trend. Metabolic pathway enrichment analysis showed that the intervention pathways were mainly associated with arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis, and glycerophospholipid metabolism. Through PLS regression analysis, 14 significant differential metabolites were obtained, mainly involving three metabolic pathways: arachidonic acid metabolism, biosynthesis of unsaturated fatty acids and glycerophospholipid metabolism. The established efficacy evaluation method indicated that Tianma Gouteng Decoction showed the most significant intervention effect, which was consistent with the theory of traditional Chinese medicine. This study discovered the common factors of formulas containing Uncaria rhynchophylla in intervening hypertension with liver Yang hyperactivity syndrome, and revealed the metabolic basis of the correspondence between these formulas and liver Yang hyperactivity syndrome. The efficacy evaluation method was built to objectively quantify formulas containing Uncaria rhynchophylla, and offers evidence for clinical research.

     

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