论文部分内容阅读
目的探索中药复方药效物质基础研究方法。方法以活血化瘀中药复方“脑得生”为研究对象,以大鼠血液流变学特性为药效学指标,将中药复方中各指标成分(有效成分)的血浆浓度与相关药效学指标进行药代动力学-药效动力学(pharmacokinetics-pharmacodynamics,PK-PD)线性模型相关分析,确定各指标成分对药效学指标的贡献,并以其贡献为权重,对各指标成分的血浆浓度进行加权组合,以组合血药浓度(表观药效浓度)与药效学指标进行线性模型相关分析,阐述中药复方的药效物质基础。结果大鼠静脉注射给予“脑得生”后,在其全血黏度发生改变的时间段(1.5～4.0 h)内,指标成分大豆苷元的血浆浓度与大鼠的全血黏度下降存在显著的正相关(r2=0.780～0.943);人参皂苷Rg1(r2=0.594～0.815)和三七皂苷R1(r2=0.559～0.739)存在负相关;其他指标成分无显著相关性,而在血液流变学考察的整个时间区间(0.5～4.0 h)内,血浆中大豆苷元浓度与全血黏度的下降无显著相关性(r2=0.0013～0.0365)。但大豆苷元、人参皂苷Rg1和三七皂苷R1的“组合血药浓度”与全血黏度的下降存在显著的相关性(r2=0.797～0.908)。结论 “组合药代动力学”(combinatorial pharmacokinetics,CPK)与药效动力学(pharmacodynamics,PD)具有良好的相关性,“组合药代动力学”及其与药效动力学的CPK-PD线性模型拟合,为中药复方药效物质基础及其配伍规律的阐明提供了方法学基础。
Objective To explore the basic research methods of traditional Chinese medicine compound pharmacodynamics. Methods Taking the compound of Chinese herbal medicine for promoting blood circulation and removing blood stasis as the research object and the hemorheological characteristics of rats as the pharmacodynamic indexes, the plasma concentrations of each index component (active ingredient) The pharmacokinetic-pharmacodynamic (PK-PD) linear model correlation analysis was used to determine the contribution of each index component to the pharmacodynamic indicators. The contribution of each index component to the pharmacodynamic indicator was determined. Plasma concentration were weighted combination of the combination of plasma concentration (apparent pharmacodynamic concentration) and pharmacodynamic indicators of linear model-related analysis, elaborated the pharmacological substance basis of traditional Chinese medicine compound. Results After intravenous injection of “brain natriuretic”, the plasma concentration of daidzein, an indicator component, declined in the whole blood of rats with the change of whole blood viscosity (1.5 ~ 4.0 h) (R2 = 0.594-0.815) and notoginsenoside R1 (r2 = 0.559-0.739). There was no significant correlation between the other indexes and the correlation between blood flow During the whole study period (0.5-4.0 h), there was no significant correlation between the concentration of daidzein in plasma and the decrease of whole blood viscosity (r2 = 0.0013-0.0365). However, there was a significant correlation between the “combined plasma concentration” of daidzein, ginsenoside Rg1 and notoginsenoside R1 and the decrease of whole blood viscosity (r2 = 0.797-0.908). Conclusions There is a good correlation between combinatorial pharmacokinetics (CPK) and pharmacodynamics (PD), “combinatorial pharmacokinetics” and its relationship to pharmacodynamics CPK -PD linear model fitting provides the methodological foundation for the elucidation of the pharmacodynamic basis and compatibility of traditional Chinese medicine.