单向在体肠灌流模型研究“丹参-红花药对”中主要活性成分肠转运特征  

Intestinal Transit Characteristics Study of Danshen-Honghua Drug Pairs through In Vivo Single-Pass Intestinal Perfusion Rat Model

作　　者：白吉庆[1] 王鹏飞 王小平[1] 胡锦萍[1] 王亚恒[1] 王金[1] Bai Jiqing;Wang Pengfei;Wang Xiaoping;Hu Jinping;Wang Yaheng;Wang Jin(Shaanxi University of Traditional Chinese Medicine,Xianyang 712046)

机构地区：[1]陕西中医药大学,咸阳712046

出　　处：《中药药理与临床》2020年第4期149-153,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：陕西省科技厅社发项目(编号:2019SF-286);陕西省教育厅重点实验室项目(编号:18JS025);国家自然科学基金委项目(编号:81974544)。

摘　　要：目的:探讨丹参-红花药对中主要活性成分的肠吸收特征。方法:采用大鼠在体单向肠灌流模型,以吸收速率常数(Ka)和表观吸收系数(Papp)为评价指标,研究丹酚酸B、羟基红花黄色素A两个主要成分在十二指肠、空肠、回肠和结肠不同肠段的吸收情况;在吸收最佳的肠段考察质量浓度、P-糖蛋白(P-gp)抑制剂盐酸维拉帕米、多药耐药蛋白相关蛋白2(MRP2)抑制剂丙磺舒和能量抑制剂2,4-二硝基苯酚对上述两个成分肠吸收的影响。结果:丹酚酸B和羟基红花黄色素A在各肠段均有吸收,且回肠的吸收最佳;在回肠段:丹酚酸B和羟基红花黄色素A的吸收在实验质量浓度范围内(2 mg/mL^6 mg/mL)具有浓度依赖性;和不含抑制剂的组比较,盐酸维拉帕米(100 mg/mL),丙磺舒(12 mg/mL, 24 mg/mL)和2,4-二硝基苯酚(20 mg/mL^60 mg/mL)对丹酚酸B和羟基红花黄色素A的Ka和Papp均有明显影响(P<0.05)。结论:在回肠段:在实验浓度范围内丹酚酸B和羟基红花黄色素A的吸收均有能量依赖性,吸收机制可能属于主动吸收;丹酚酸B和羟基红花黄色素A可能是P-糖蛋白和多药耐药蛋白相关蛋白2的底物。Objective:To explore the intestinal absorption characteristics of main active ingredients in Danshen-Honghua drug-pairs. Methods:Rat in vivo single-pass perfusion method was used. The absorption rate constant(Ka) and the apparent absorption coefficient(Papp) were used to study the intestinal absorption characteristics of salvianolic acid B and hydroxysafflor yellow A, in duodenum, jejunum, ileum, and colon. In the optimal absorption intestinal site, the effects of different concentrations of drugs were observed, the influences of verapamil hydrochloride(P-glycoprotein inhibitor), probenecid(multi-drug resistant protein inhibitor, MRP2 inhibitor) and 2,4-dinitrophenol on salvianolic acid B and hydroxysafflor yellow A were studied.Results:Salvianolic acid B and hydroxysafflor yellow A were absorbed at all four intestinal segments, and the optimal absorption site was the ileum. The absorptions of salvianolic acid B and hydroxysafflor yellow A were concentration-dependent in the range of experimental concentrations(2 mg/ml^6 mg/ml) in ileum. Compared with the group without inhibitor, Verapamil hydrochloride(100 mg/L), Probenecid(12 mg/L, 24 mg/L), and 2,4-dinitrophenol(20 mg/ml^60 mg/ml)(100 mg/L) had the significant influence on K a and P app of salvianolic acid B and hydroxysafflor yellow A(P<0.05). Conclusion:In the ileum part, the absorptions of salvianolic acid B and hydroxysafflor yellow A are energy-dependent in the range of experimental concentrations, and the absorption mechanism may be the active diffusion transport. Salvianolic acid B and hydroxysafflor yellow A may be the substrate of multi-drug resistant protein and P-glycoprotein in ileum.

关 键 词：丹参-红花药对 在体单向肠灌流 肠吸收 丹酚酸B 羟基红花黄色素A 

分 类 号：R285.5[医药卫生—中药学]