[关键词]
[摘要]
目的 研究当归-川芎药对超临界提取物(AC-SFE)配伍红花不同提取物的HPLC指纹图谱及其抗心肌缺血作用的谱效关系。方法 采用结扎大鼠冠状动脉致急性心肌缺血的模型,运用双变量相关分析(BCA)和多元回归分析(MRA),将AC-SFE与红花各配伍组合的药效数据与指纹图谱共有峰的相对峰面积相关联,并采用LC-MS指认色谱峰。结果 来自AC-SFE的8个色谱峰与大鼠心肌梗死面积比率及血清乳酸脱氢酶(LDH)呈负相关,其中4个呈显著负相关;来自红花中的8号峰(槲皮素-3-O-β-D-半乳糖苷-4′-O-β-D-吡喃葡萄糖苷)则与药效呈现显著正相关。强迫引入法回归分析显示有4个峰进入回归曲线方程。LC-MS共指认出16个色谱峰,其中12个是相关峰。结论 AC-SFE中的阿魏酸(峰13)、洋川芎内酯H(峰15)、3-羟基丁基苯酞(峰16)、洋川芎内酯A(峰18)、3-丁基苯酞(峰19)、藁本内酯(峰20)、二丁基苯酞(峰21)、苯酞类化合物(峰17)以及红花中的峰1(4-methoxy-6-[3, 4, 5-trihydroxy-6-[[3, 4, 5-trihydroxy-6 (hydroxymethyl) tetra- hydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]oxy-cyclohexane-1, 2, 3, 5-tetrol)和峰2(3-{[6-O-(D-galactopyranosyl)-β-D-galac- topyranosyl]oxy}-1, 2-propanediyl diacetate)可能是抗心肌缺血的药效物质;而峰8可能不能缓解心肌缺血。
[Key word]
[Abstract]
Objective To study the spectrum-activity relationships between the anti-myocardial ischaemia activity and the HPLC fingerprints of the formula, consisting of Angelicae Sinensis Radix-Chuanxiong Rhizoma supercritical fluid extraction (AC-SFE) and Carthami Flos (CF) solvent-extracted extracts. Methods The rat model of acute myocardial ischemia was established by applying left anterior descending coronary ligation, and bivariate correlation analysis (BCA) and multivariate regression analysis (MRA) were used to investigate the spectrum-activity relationship between fingerprints and anti-myocardial ischaemia activity. LC-MS was used for peak assignment. Results Eight peaks of AC-SFE were negatively correlated with the infarct size ratio (ISR) and the serum lactate dehydrogenase (LDH), and four of them were significantly correlated. Peak 8 (quercetin-3-O-β-D-galactose glycosides-4′-O-β-D-pyranglucoside) from CF was positively correlated with the efficacy. Study by regression analysis showed four peaks were in regression equations. LC-MS showed 16 peaks, among which 12 were correlated peaks. Conclusion Ferulic acid (peak 13), senkyunolide H (peak 15), 3-hydroxy butylphthalide (peak 16), senkyunolide A (peak 18), 3-butylphthalide (peak 19), ligustilide (peak 20), dibutyl phthalide (peak 21), and phthalide ( peak 17 ) of AC-SFE and peak 1 (4-methoxy-6-[3, 4, 5-trihydroxy-6-[[3, 4, 5-trihydroxy-6 (hydroxymethyl) tetra-hydropyran-2-yl]oxymethyl] tetrahydropyran-2-yl]oxy-cyclohexane-1, 2, 3, 5-tetrol) and peak 2 (3-{[6-O-(D-Galactopyranosyl)-β-D-galacto-pyrano-syl]oxy}- 1,2-propanediyl diacetate) of CF might be the material foundation for the anti-myocardial ischaemia activity. Peak 8 might not be able to relieve myocardial ischaemia.
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[基金项目]
国家“重大新药创制”科技重大专项“十一五”计划资助项目(20092x09301-007)