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一药效动力学(pharmacoldnefics-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(1.5~4.0h)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(0.5~4.0h)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Rg,和三七皂苷R,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 pharmacokinefics,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 establish a method to illuminate the therapeutical basis of traditional Chinese medicine ( TCM ) recipe. Methods The plasma" combinatorial concentrations" of mark ingredients ( markers ) in the Naodesheng are combined with the hemorheological properties of blood in rats, which are the clinical syndromes of effects of Naodesheng on activating blood circulation to dissipate blood stasis, to establish a linear correlation model between combinatorial pharmacokinetics (CPK) and pharmacodynamics (PD). Results The plasma concentrations of daidzein showed a remarkable positive correlation with the depression of the blood viscosity( r2 = 0. 780-0. 943 ) while that of gensenoside Rg1 (r2 = 0. 594-0. 815 ) and notoginsenoside R1 (rE = 0. 559-0. 739 ) showed strongly negative correlations with the change of blood viscosity (from 1.5 to 4 hour) after iv administration of Naodesheng injection in rats. Other markers showed no significant correlations. In the whole period from 0.5 to 4 hour while the hemorheological properties were observed, the plasma concentration of daidzein showed slightly negative correlation with the blood viscosity( r2 = 0. 001 3- 0. 036 5 ) while" combinatorial concentrations" of daidzein, gensenoside Rg1 and notoginsenoside R1 showed significant positive correlations ( r2 = 0. 797- 0. 908 ) with the depression of blood viscosity. Conclusions The plasma" combinatorial concentration" has significant correlation with the clinical syndromes of TCM recipe. The CPK-PD linear model should be introduced into the pharmacokinetic research on TCM recipe. The "combinatorial pharmacokinetics" will provide a method to illuminate the therapeutical basis and the rule of compatibility of TCM recipe.