防风对痛泻要方活性成分在正常大鼠体内的药动学和组织分布的影响(1)
[摘要] 痛泻要方是治疗肝脾不和之痛瀉的经典方剂，方中防风具有引经作用。该研究采用超高效液相色谱串联质谱(UPLC-MS/MS)，以正负离子切换，多反应监测模式(MRM)同时测定大鼠灌胃不同配伍痛泻要方后血浆和组织中4种活性成分，比较不同配伍之间4种活性成分药动学和组织分布差异，探讨防风对痛泻要方主要成分的影响。研究发现，防风可提高芍药苷、橙皮苷的Cmax，AUC0-t，AUC0-∞，增加肝、脾、脑和小肠中白术内酯Ⅰ、芍药苷、橙皮苷的分布浓度，减少肺中白术内酯Ⅰ和没食子酸的分布；通过计算组织与血浆中的药物浓度比发现，防风可显著提高白术内酯Ⅰ、芍药苷、橙皮苷的脑/血浆比，降低白术内酯Ⅰ、芍药苷的肺/血浆比和芍药苷的脾/血浆比，推测防风可能通过增加痛泻要方有效成分的脑分布发挥引经作用。
[关键词] 防风； 痛泻要方； 药代动力学； 组织分布； 引经
[Abstract] Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However， the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs， we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis . The results revealed that Saposhnikoviae Radix could enhance Cmax， AUC0-t， and AUC0-∞ of paeoniflorin and hesperidin， and increase the distribution of atractylenolide-I， paeoniflorin and hesperidin in liver， spleen， brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I， paeoniflorin and hesperidin. Meanwhile， it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix， and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.
, 百拇医药
[Key words] Saposhnikoviae Radix； Tongxie Yaofang； pharmacokinetic； tissue distribution； meridian guiding
痛泻要方由炒白术、炒白芍、炒陈皮、防风组成，最早见于《丹溪心法》，为治疗肝脾不和之痛泻的经典方剂，现在常用于肠易激综合征、结肠炎等[1-2]。历代医家分析痛泻要方均认为，防风辛能疏散肝风，香可舒脾，又作为脾经引经之药，为该方佐使药。中医理论认为，引经药可改变其他药物的作用方向，使其作用侧重或集中于特定的部位，使药效靶向集中，提高疗效。现代研究表明引经药可通过增加靶组织中药物分布浓度而增强疗效[3]。因此，本实验拟通过评价防风对痛泻要方活性成分药代动力学的影响，比较不同组方间药物组织分布的差异，为阐明防风的引经作用及机制提供依据。
1 材料
, 百拇医药
1.1 仪器与试剂
Acquity UPLC超高效液相色谱仪、Xevo TQS三重四极杆串联质谱仪(美国Waters公司)，2K15型高速离心机(Sigma公司)，AE240电子分析天平(瑞士Mettler公司)，T18型匀浆机(德国IKA公司)。
炒白术、炒白芍、炒陈皮、防风购自河南省顺康医药有限公司，经河南省中医药研究院王慧森副研究员鉴定分别为菊科植物白术Atractylodes macrocephala Koidz. 的干燥根茎，毛茛科植物芍药Paeonia lactiflora Pall. 的干燥根，芸香科植物橘Citrus reticulata Blanco. 的成熟果皮和伞形科植物防风Saposhnikovia divaricata (Turcz.) Schischk. 的干燥根。白术内酯Ⅰ(111975-201501)、芍药苷(110736-201438)、没食子酸(110831-201605)、橙皮苷(110721-201316)、葛根素(110752-201514)、淫羊藿苷(110737-201516)购自中国食品药品检定研究院。甲醇(色谱纯，美国TEDIA公司)，其余试剂为分析纯。, http://www.100md.com(梁瑞峰 葛文静 魏征 张雪侠 崔伟锋 刘雪 李更生)
[关键词] 防风； 痛泻要方； 药代动力学； 组织分布； 引经
[Abstract] Tongxie Yaofang (TXYF) is a famous formula that has been used for treating gastrointestinal diseases in traditional Chinese medicine(TCM). Saposhnikoviae Radix is considered as a meridian guiding drug in TXYF and could enhance the effectiveness of prescription. However， the scientific evidence for this effect is still not clear. To reveal the interactions of Saposhnikoviae Radix with other herbs， we conducted this study on the pharmacokinetic profile and tissue distribution of active ingredients of TXYF in rats. The concentrations of four components in blood and tissues were determined by UPLC-MS/MS after oral administration with TXYF. The detection was carried out by electrospray ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. The positive and negative ion switching technique was performed in the same analysis . The results revealed that Saposhnikoviae Radix could enhance Cmax， AUC0-t， and AUC0-∞ of paeoniflorin and hesperidin， and increase the distribution of atractylenolide-I， paeoniflorin and hesperidin in liver， spleen， brain and small intestine. Saposhnikoviae Radix increased the ratio of brain to blood concentrations of atractylenolide-I， paeoniflorin and hesperidin. Meanwhile， it reduced the ratio of lung to blood concentrations of atractylenolide-I and paeoniflorin. Saposhnikoviae Radix， and may enhance the effectiveness of prescriptions by promoting distribution of other herbs in brain.
, 百拇医药
[Key words] Saposhnikoviae Radix； Tongxie Yaofang； pharmacokinetic； tissue distribution； meridian guiding
痛泻要方由炒白术、炒白芍、炒陈皮、防风组成，最早见于《丹溪心法》，为治疗肝脾不和之痛泻的经典方剂，现在常用于肠易激综合征、结肠炎等[1-2]。历代医家分析痛泻要方均认为，防风辛能疏散肝风，香可舒脾，又作为脾经引经之药，为该方佐使药。中医理论认为，引经药可改变其他药物的作用方向，使其作用侧重或集中于特定的部位，使药效靶向集中，提高疗效。现代研究表明引经药可通过增加靶组织中药物分布浓度而增强疗效[3]。因此，本实验拟通过评价防风对痛泻要方活性成分药代动力学的影响，比较不同组方间药物组织分布的差异，为阐明防风的引经作用及机制提供依据。
1 材料
, 百拇医药
1.1 仪器与试剂
Acquity UPLC超高效液相色谱仪、Xevo TQS三重四极杆串联质谱仪(美国Waters公司)，2K15型高速离心机(Sigma公司)，AE240电子分析天平(瑞士Mettler公司)，T18型匀浆机(德国IKA公司)。
炒白术、炒白芍、炒陈皮、防风购自河南省顺康医药有限公司，经河南省中医药研究院王慧森副研究员鉴定分别为菊科植物白术Atractylodes macrocephala Koidz. 的干燥根茎，毛茛科植物芍药Paeonia lactiflora Pall. 的干燥根，芸香科植物橘Citrus reticulata Blanco. 的成熟果皮和伞形科植物防风Saposhnikovia divaricata (Turcz.) Schischk. 的干燥根。白术内酯Ⅰ(111975-201501)、芍药苷(110736-201438)、没食子酸(110831-201605)、橙皮苷(110721-201316)、葛根素(110752-201514)、淫羊藿苷(110737-201516)购自中国食品药品检定研究院。甲醇(色谱纯，美国TEDIA公司)，其余试剂为分析纯。, http://www.100md.com(梁瑞峰 葛文静 魏征 张雪侠 崔伟锋 刘雪 李更生)