摘要
研究白芷提取物对黄芩苷肠吸收的影响,初步探讨白芷促进黄芩苷吸收的机制。采用大鼠外翻肠囊模型研究黄芩苷在十二指肠、空肠、回肠及结肠的吸收特点,以及白芷对黄芩苷不同肠段吸收的影响,确定最佳促吸收部位;采用在体单向肠灌流模型研究黄芩苷不同浓度在最佳促吸收部位的吸收特性和白芷对黄芩苷的促吸收作用;建立大鼠肠灌流后肝门静脉取血模型,分析血中药物浓度,进一步验证白芷对黄芩苷的促吸收作用。结果发现黄芩苷吸收顺序为:回肠>结肠>空肠>十二指肠。加入白芷后十二指肠的吸收显著增加,因此选择十二指肠为研究肠段。黄芩苷在十二指肠的表观通透系数(Papp)和吸收速率常数(Ka)随着浓度的增加而逐渐增加,当浓度达到一定时,吸收具有自身浓度抑制作用,说明黄芩苷吸收机制可能是载体中介转运。加入盐酸维拉帕米后,黄芩苷的Papp和Ka值基本保持不变,说明黄芩苷可能不是P-糖蛋白(P-gp)底物。加入白芷后,两种吸收模型均表明黄芩苷在十二指肠的单位面积吸收量显著增加(P<0.01),肝门静脉血中药物分析也显示白芷可增加黄芩苷的吸收。
To explore the mechanism of the absorption enhancement of Angelica dahurica extract（Ade）,the absorption mechanism of baicalin in the Scutcllaria water extraction as well as the effect of Angelica dahurica extract on absorption of baicalin were investigated.In order to determine the main absorption site,everted intestinal sac model was used to study the effect of Angelica dahurica extract on the absorption of baicalin at duodenum,jejunum,ileum and colon.In situ single pass intestinal perfusion model was performed to study the absorption of various concentrations of baicalin and the effect of Angelica dahurica extract on the absorption of baicalin at the main absorption site.To authenticate the consequence of perfusion by getting the blood from the hepatic portal vein and determine the concentration of the baicalin in the blood.The result showed that baicalin could be absorbed at all of the four intestinal segments with increasing absorption amount per unit as follows：ileum colon jejunum duodenum.The absorption of baicalin in the duodenum significantly increased with Angelica dahurica extract,thus,duodenum was chosen to be the studying site.Apparent permeability values（Papp） and absorption rate constant（Ka） of baicalin in the duodenum increased gradually with higher concentrations.When the concentration of baicalin rises to a certain degree,the absorption increase had a saturable process,the absorption of baicalin may be an active transportation.Baicalin may be not a substrate of P-gp as verapamil which had not significantly affected the Papp and Ka of baicalin.The absorption of baicalin in the duodenum significantly increased（P0.01） in the two models with Angelica dahurica extract and the concentration of baicalin in the blood from the hepatic portal vein showed that the Angelica dahurica extract can increase the absorption of baicalin.
出处
《药学学报》
CAS
CSCD
北大核心
2011年第2期232-237,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(30960516)
重大新药创制中药新型给药系统技术平台(2009ZX09310-005)
关键词
白芷
黄芩苷
外翻肠囊
在体单向肠灌流模型
吸收机制
Angelica dahurica
baicalin
everted rat gut sacs
in situ single pass perfusion model
absorption mechanism
