目的 应用总量统计矩法研究丹红注射液主要有效成分丹参素、原儿茶醛、丹酚酸B和羟基红花黄色素A（HYSA）正交配伍对总量药动学参数的影响，研究复方内在配伍规律。方法 以改良的线栓法复制大鼠大脑中动脉栓塞（MCAO）模型，采用正交试验法L₉(3⁴)组成丹红注射液主要有效成分（丹参素、原儿茶醛、丹酚酸B、HYSA）用量配比不同的9个组方，供大鼠尾静脉iv给药，进行药动学研究。用DAS 3.2.6软件以非房室模型法拟合药动学参数，并进一步运用总量统计矩法计算总量药动学参数。应用正交分析法评价配伍对总量药动学参数的影响。结果 丹红注射液主要有效成分丹参素、原儿茶醛、丹酚酸B和HYSA正交配伍对总量统计矩各参数影响不一，总量零阶矩AUCt以丹参素水平的影响最大，且影响显著（P<0.05），最优组合为A₃B₃C₂D₁；总量一阶矩MRT_t以HYSA水平影响最大，最优组合为A₁B₃C₁D₁。结论 总量统计矩可整合丹参素、原儿茶酸、香草酸、丹酚酸B、HYSA的药动学参数，表达各组方的整体药动学行为，中药复方多成分药动学可采用总量统计矩法进行研究，可为中药复方内在配伍规律研究提供方法。

Objective Using total quantum statistical moment analysis to evaluate the influence of the main effective constituents in Danhong Injection on the total pharmacokinetic parameters after orthogonal design to research internal compatibility rule of traditional Chinese medicine (TCM) compound. Methods Using modified middle cerebral artery occlusion (MCAO) method to establish rat disease model of focal cerebral ischemia-reperfusion (I/R) injury. According to the orthogonal design L₉(3⁴) composed of the main effective constituents (danshensu, protocatechuic aldehyde, salvianolic acid B, and HYSA) of Danhong Injection, nine combinations with different dosage ratios were formed, which were used for iv administration in MCAO rats to study the pharmacokinetics of effective constituents after compatibility. Using non-compartmental model of DAS 3.2.6 software to fit the pharmacokinetic parameters and using total quantum statistical moment analysis method to calculate the main total quantum statistical moment parameters. The influence of different compatibilities on the total pharmacokinetics parameters was analyzed by orthogonal test. Results There were different effects of the main effective constituents with orthogonal compatibilities on the total quantum statistical moment parameters. Danshensu had the strongest effect on the total AUC and had a significant effect (P<0.05). A₃B₃C₂D₁ was the preferred dose combination for AUC_t. HYSA had the strongest effect on the total MRT and its optimal ingredient composition was A₁B₃C₁D₁. Conclusion The total quantum statistical moment analysis could combine the pharmacokinetics of danshensu, protocatechuic acid, vanillic acid, salvianolic acid B, and HYSA, and express the total pharmacokinetic behaviors. The total quantum statistical moment analysis method can be used to study the pharmacokinetics of multi-component in TCM compound prescription, which can provide the method for research on internal compatibility rule for TCM compound.

国家自然科学基金资助项目（81630105，81274176，81473587）；浙江省自然科学基金资助项目（LR16H270001，LZ17H270001）