大鼠体内泻心汤及其不同配伍黄酮类成分药代动力学变化规律探究.docVIP

大鼠体内泻心汤及其不同配伍黄酮类成分药代动力学变化规律探究 　 作者：周慧，马越鸣　石荣，闫晶超 【摘要】 目的研究泻心汤不同配伍黄酮类成分在大鼠体内药代动力学的差异。方法大鼠随机分为4组，分别灌胃给予泻心汤(XXD)，单味黄芩(RS)，大黄+黄芩(RRR+RS)和黄连+黄芩(CC+RS)，给药前及给药后不同时间采集血样，HPLC法测定黄芩苷和汉黄芩苷浓度，由血药浓度-时间数据计算药动学参数，比较组间差异。结果与RS组相比，其余3组中黄芩苷的AUC和Cmax数值均有不同程度的降低;而CC+RS组中汉黄芩苷的AUC和Cmax数值与RS组相比亦有明显减少。结论泻心汤配伍(黄连和大黄)可能使黄芩中黄芩苷和汉黄芩苷的吸收减少、暴露水平降低，其中黄连的影响更明显。 【关键词】 泻心汤; 黄酮类; 配伍; 药代动力学 　　Abstract：ObjectiveTo investigate the pharmacokinetic profile of the baicalin and wogonoside in rats after oral administration of Xiexin Decoction (XXD)and the different combinations of its constituent herbs. MethodsRats were divided into four groups and were randomly administered one of the four aquous extracts: RS, RS + RRR, RS+CC and XXD (RS+RRR+CC) via intragastric gavage. Plasma concentrations of Baicalin and wogonoside were measured by HPLC. Pharmacokinetic parameters were calculated from the plasma concentration-time data.ResultsThe Cmax and AUC of baicalin and wogonoside were significantly different among the four groups. Compared with the group of RS alone, the rest three groups, RS+CC, RS + RRR and RS+RRR+CC (XXD), showed a decrease in AUC and Cmax of the baicalin and RS+CC group showed a decrease in the AUC and Cmax of wogonoside.ConclusionThe results suggested that CC and RRR may markedly decrease the absorption and systematic exposure levels of baicalin and wogonoside in RS, and CC has more profound effect. 　　Key words： Xiexin Decoction; Flavonoids; Compatibility; Pharmacokinetics 　　泻心汤(Xiexin Decoction)为出自《金匮要略》的清热经典名方，由大黄、黄芩、黄连组成，具有抗炎[1]、抗病原微生物、抗凝、改善高血压及高脂血症、保护胃黏膜等药理作用[2]。关于泻心汤配伍成分的研究报道有很多，如应用HPLC测定黄芩苷-小檗碱沉淀物在不同条件下的平衡浓度[3]等。但是在泻心汤不同配伍中黄酮成分的药代动力学研究未见报道。 　　黄芩(Radix Scutellariae)为唇形科植物黄芩Scutellria baicalensis Georgi.的干燥根。味苦，性寒，具有清热燥湿，泻火解毒之功效。黄芩有效成分为黄酮类，主要包括黄芩苷(baicalin)、黄芩素(baicalein)、汉黄芩苷(wogonoside)、汉黄芩素(wogonin)等(图1)。文献报道，黄芩苷由于极性大不能直接跨膜转运吸收入血，而是在肠道菌群的葡萄糖醛酸苷酶作用下转化为其苷元即黄芩素，黄芩素进入肠黏膜后，在UDPG-葡萄糖醛酸转移酶的作用下转化为黄芩素-葡萄糖醛酸结合物(恰好与原型黄芩苷结构一致)，再主要以黄芩苷的形式经肠道吸收入血，进入血液的黄芩素还可在肝脏经UDPG-葡萄糖醛酸转移酶转化生成黄芩素-葡萄糖醛酸结合物(即黄芩苷)[4～8