细胞膜色谱法筛选川芎—白芷中5—HT受体激动剂的研究(1)
[摘要]偏头痛是临床的常见病和多发病，研究表明，5-羟色胺(5-HT)受体在偏头痛的发病中起重要作用。实验通过大鼠纹状体组织制备得到色谱固定相，并利用细胞膜色谱与液相色谱的离线联用来特异性地识别川芎-白芷药对中可与固定相上受体相互作用的配体，发现了欧前胡素是其中潜在的活性成分。以不同浓度(2.42×10-8～4.84×10-7 mol·L-1)的5-HT1D受体激动剂舒马普坦为模型药物，记录样品在模型中的容量因子，测得欧前胡素与5-HT1D受体作用的平衡解离常数为(4.59±0.33)×10-6 mol·L-1，并采用硝酸甘油致大鼠偏头痛模型验证其药理活性。该研究为体外快速有效地研究药物与受体之间的相互作用提供了一种新方法。
[关键词]川芎;白芷;纹状体;细胞膜色谱;5-羟色胺受体;偏头痛
[收稿日期]2014-08-10
, 百拇医药
[基金项目]陕西省中医药管理局科研项目(13-ZY005)
[通信作者]*杜晖，博士，主管药师，Tel：(029)85535544，E-mail： duhui0504@126.comA cell membrane chromatography method for screening 5-HT receptor agonists
from drug pair of Chuanxiong Rhizoma and Angelicae Dahuricae Radix
DU Hui1*， LV Nan2， HUANG Jie1， DENG Mei1
(1. Xi′an Institute for Food and Drug Control， Xi′an 710054， China;
, 百拇医药
2. Health Science Center， Xi′an Jiaotong University， Xi′an 710061， China)
[Abstract]Migraine is one of the common and frequently encountered diseases. The study proves that 5-hydroxytryptamine (5-HT) receptor， plays an important role in the occurrence of migraine. Rat striatum was used for preparation of the cell membrane stationary phase (CMSP) in our experiments. The cell membrane chromatography (CMC)-offline-HPLC system was applied to specifically recognize the components from the drug pair of Chuanxiong Rhizoma and Angelicae Dahuricae Radix， which interact with the receptors on CMSP. The dissociation equilibrium constant (KD) was measured in a rat striatum/CMC system， performed by continuously pumping sumatriptan， a 5-HT1D agonist， ranging from 2.42×10-8 to 4.84×10-7 mol·L-1 through a CMC column， and the capacity factors (k′) were recorded. The KD value obtained from the model was (4.59 ± 0.33)×10-6 mol·L-1 for imperatorin， and the rat model of migraine induced by nitroglycerin was applied to validate the pharmacological effects of the drug pair. The results indicated that the CMC method could be a quick and efficient way for characterizing the drug-receptor interactions in vitro.
, 百拇医药
[Key words]Chuanxiong Rhizoma; Angelicae Dahuricae Radix; striatum; cell membrane chromatography; 5-hydroxytryptamine receptor; migraine
doi：10.4268/cjcmm20150322
偏头痛是临床上的常见疾病，也是致残性最高的一种慢性疾病[1]。偏头痛的发病机制非常复杂，其病理机制至今没有完全清楚。众多研究表明，5-羟色胺(5-HT)在偏头痛的发病过程中起着很重要的作用[2-3]。但是目前现有5-HT受体激动剂种类很少，均有不同程度的不良反应，不适于长期使用[4-6]。川芎、白芷配伍是治疗偏头痛最为常用的药对之一，在都梁丸[7-8]、芷芎散[9]等众多古方中均有记载，但川芎-白芷药对在治疗偏头痛中配伍比例及协同作用机制尚不明确。, 百拇医药(杜晖 吕楠 黄洁 邓梅)
[关键词]川芎;白芷;纹状体;细胞膜色谱;5-羟色胺受体;偏头痛
[收稿日期]2014-08-10
, 百拇医药
[基金项目]陕西省中医药管理局科研项目(13-ZY005)
[通信作者]*杜晖，博士，主管药师，Tel：(029)85535544，E-mail： duhui0504@126.comA cell membrane chromatography method for screening 5-HT receptor agonists
from drug pair of Chuanxiong Rhizoma and Angelicae Dahuricae Radix
DU Hui1*， LV Nan2， HUANG Jie1， DENG Mei1
(1. Xi′an Institute for Food and Drug Control， Xi′an 710054， China;
, 百拇医药
2. Health Science Center， Xi′an Jiaotong University， Xi′an 710061， China)
[Abstract]Migraine is one of the common and frequently encountered diseases. The study proves that 5-hydroxytryptamine (5-HT) receptor， plays an important role in the occurrence of migraine. Rat striatum was used for preparation of the cell membrane stationary phase (CMSP) in our experiments. The cell membrane chromatography (CMC)-offline-HPLC system was applied to specifically recognize the components from the drug pair of Chuanxiong Rhizoma and Angelicae Dahuricae Radix， which interact with the receptors on CMSP. The dissociation equilibrium constant (KD) was measured in a rat striatum/CMC system， performed by continuously pumping sumatriptan， a 5-HT1D agonist， ranging from 2.42×10-8 to 4.84×10-7 mol·L-1 through a CMC column， and the capacity factors (k′) were recorded. The KD value obtained from the model was (4.59 ± 0.33)×10-6 mol·L-1 for imperatorin， and the rat model of migraine induced by nitroglycerin was applied to validate the pharmacological effects of the drug pair. The results indicated that the CMC method could be a quick and efficient way for characterizing the drug-receptor interactions in vitro.
, 百拇医药
[Key words]Chuanxiong Rhizoma; Angelicae Dahuricae Radix; striatum; cell membrane chromatography; 5-hydroxytryptamine receptor; migraine
doi：10.4268/cjcmm20150322
偏头痛是临床上的常见疾病，也是致残性最高的一种慢性疾病[1]。偏头痛的发病机制非常复杂，其病理机制至今没有完全清楚。众多研究表明，5-羟色胺(5-HT)在偏头痛的发病过程中起着很重要的作用[2-3]。但是目前现有5-HT受体激动剂种类很少，均有不同程度的不良反应，不适于长期使用[4-6]。川芎、白芷配伍是治疗偏头痛最为常用的药对之一，在都梁丸[7-8]、芷芎散[9]等众多古方中均有记载，但川芎-白芷药对在治疗偏头痛中配伍比例及协同作用机制尚不明确。, 百拇医药(杜晖 吕楠 黄洁 邓梅)