黑顺片血浆指纹图谱与抗心衰作用的谱效关系研究

Spectrum-effect relationship between fingerprint in plasma of Heishunpian and its anti-heart failure effect

目的探讨ig黑顺片(附子炮制品)醇提物后大鼠血浆指纹图谱与药效指标(血压、心率)间的谱效关系,以阐明附子抗心衰作用的药效物质基础。方法利用UPLC-QTOF/MS建立大鼠ig黑顺片醇提物的血浆指纹图谱,并连续监测心衰大鼠的血压和心率,再用偏最小二乘回归(PLSR)法对黑顺片入血成分指纹峰与药效指标进行相关性分析。结果从黑顺片血浆指纹图谱中筛选出13个入血成分,通过PLSR分析发现次乌头原碱、苯甲酰中乌头原碱、苯甲酰次乌头原碱和3,13-脱氧苯甲酰乌头原碱的血浆药物浓度变化与心率或血压变化呈显著正相关性,且VIP值大于1。结论次乌头原碱、苯甲酰中乌头原碱、苯甲酰次乌头原碱和3,13-脱氧苯甲酰乌头原碱为黑顺片抗心衰作用的潜在药效物质。

Objective To investigate the spectrum-effect relationship between the fingerprint in plasma of Heishunpian （black-processed pieces of Aconit Lateralis Radix Praeparata） and its pharmacodynamic parameters （blood pressure and heart rate） after ig administration to rats, and to elucidate its effective substances. Methods Ultra performance liquid chromatography with quadrupole and time-of-flight mass spectrometry （UPLC-QTOF/MS） was used for fingerprint profiling by analyzing plasma samples obtained after ig administration of the ethanol extract from Heishunpian to rats. Meanwhile, the blood pressure and heart rate of heart-failure rats were continuously monitored and recorded. The relationship between the absorbed fingerprint and pharrnacodynamic parameters of Heishunpian was established by correlation analysis with partial least square regression （PLSR） method. Results Atotal of 13 alkaloids were detected in rat plasma, among which hypaconine, benzoylmesaconitine, benzoylhypaconitine, and 3,13-deoxybenzoylaconitine were found to be significantly and positively related to the pharmacodynamic data with VIP 〉 1. Conclusion Hypaconine, benzoylmesaconitine, benzoylhypaconitine, and 3,13- deoxybenzoylaconitine are potential effective substances with anti-heart failure effects ofHeishunpian.