单向灌流法研究巴戟天低聚糖的大鼠肠吸收特性(1)
[摘要]采用大鼠在体肠单向灌流实验模型，利用HPLC-ELSD测定肠灌流液中蔗糖、蔗果三糖、耐斯糖、1F-果呋喃糖基耐斯糖和巴戟甲素等5种低聚糖的含量，研究各低聚糖在小肠段(十二指肠、空肠、回肠)和结肠的吸收情况，并考察药物浓度、灌流液pH以及P-糖蛋白(P-gp)抑制剂对药物吸收的影响，得出各低聚糖成分在大鼠体内的肠吸收机制。结果显示5种低聚糖均为全肠道吸收的药物，吸收速率与灌流液pH、药物浓度和肠段部位有关。盐酸维拉帕米可显著增加蔗糖与巴戟甲素的吸收量，提示蔗糖与巴戟甲素是P-gp的底物。5种低聚糖在大鼠肠道内的吸收机制以被动扩散方式为主，不存在饱和吸收，其在全肠段的吸收均较好，吸收部位主要在十二指肠和空肠。
[关键词]巴戟天低聚糖;肠吸收;单向灌流法;P-糖蛋白
[收稿日期]2014-05-14
[基金项目]国家自然科学基金项目(81403085);东莞市医疗卫生科技计划一般项目(2014105101295);广东医学院科研基金博士学位人员科研启动项目(B2013007)
, http://www.100md.com
[通信作者]*林励，研究员，博士生导师，研究方向为中药资源开发利用与新药研究，Tel：(020)39358270，E-mail：LL76611@126.com
[作者简介]邓少东，讲师，博士，研究方向为中药资源开发利用与新药研究，E-mail：donggdyxy@163.com
Study on intestinal absorption features of oligosaccharides in
Morinda officinalis How.with sigle-pass perfusion
DENG Shao-dong1， ZHANG Peng2， LIN Li2*， XIAO Feng-xia2， LIN Jing-ran2
(1.The Second School of Clinical Medicine， Guangdong Medical College， Dongguan 523808， China;
, 百拇医药
2. College of Chinese Materia Medica， Guangzhou University of Traditional Chinese Medicine， Guangzhou 510006， China)
[Abstract]To study the in situ intestinal absorption of five oligosaccharides contained in Morinda officinalis How. (sucrose， kestose， nystose， 1F-Fructofuranosyinystose and Bajijiasu). The absorption of the five oligosaccharides in small intestine (duodenum， jejunum and ileum) and colon of rats and their contents were investigated by using in situ single-pass perfusion model and HPLC-ELSD. The effects of drug concentration， pH in perfusate and P-glycoprotein inhibitor on the intestinal absorption were investigated to define the intestinal absorption mechanism of the five oligosaccharides in rats. According to the results， all of the five oligosaccharides were absorbed in the whole intestine， and their absorption rates were affected by the pH of the perfusion solution， drug concentration and intestinal segments. Verapamil Hydrochloride could significantly increase the absorptive amount of sucrose and Bajijiasu， suggesting sucrose and Bajijiasu are P-gp′s substrate. The five oligosaccharides are absorbed mainly through passive diffusion in the intestinal segments， without saturated absorption. They are absorbed well in all intestines and mainly in duodenum and jejunum.
, 百拇医药
[Key words]oligosaccharide extracted from Morinda officinalis; intestinal absorption; single-pass intestinal perfusion; P-glycoprotein
doi：10.4268/cjcmm20150126
巴戟天为茜草科植物巴戟天Morinda officinalis How. 的肉质根，归肾、肝经，具有补肾助阳之功效，自古被誉为“补肾阳之要药”，已证实巴戟天糖类物质含量近50%，其中以低聚糖类成分为主[1]。近期药效研究表明，巴戟天低聚糖(oligosaccharide extracted from Morinda officinalis，OMO)可显著提高拟痴呆大鼠的学习记忆能力[2]、改善痴呆症状[3]，其中巴戟甲素、耐斯糖等低聚糖单体活性成分也显示具有神经细胞保护作用[4]、抗抑郁[5]、抗骨质疏松[6]等多种生物活性，表明巴戟天低聚糖类成分具有显著的开发利用前景。目前，以巴戟天为原料开发出的药品均以口服剂型为主，如巴戟天寡糖胶囊、巴戟口服液等，然而关于巴戟天低聚糖的胃肠道吸收机制研究的报道较少。因此，本研究采用大鼠在体肠单向灌流模型考察该巴戟天低聚糖有效部位中蔗糖、蔗果三糖、耐斯糖、1F-果呋喃糖基耐斯糖和巴戟甲素等5种低聚糖类成分的大鼠肠吸收特点，以揭示巴戟天低聚糖类成分的肠道吸收机制，确定各成分的最佳吸收部位，并考察了P-gp对巴戟天低聚糖类成分吸收的影响，以期为巴戟天低聚糖类药物的剂型开发及其在临床上的合理用药提供科学依据。, 百拇医药(邓少东 张鹏 林励 肖凤霞 林靖然)
[关键词]巴戟天低聚糖;肠吸收;单向灌流法;P-糖蛋白
[收稿日期]2014-05-14
[基金项目]国家自然科学基金项目(81403085);东莞市医疗卫生科技计划一般项目(2014105101295);广东医学院科研基金博士学位人员科研启动项目(B2013007)
, http://www.100md.com
[通信作者]*林励，研究员，博士生导师，研究方向为中药资源开发利用与新药研究，Tel：(020)39358270，E-mail：LL76611@126.com
[作者简介]邓少东，讲师，博士，研究方向为中药资源开发利用与新药研究，E-mail：donggdyxy@163.com
Study on intestinal absorption features of oligosaccharides in
Morinda officinalis How.with sigle-pass perfusion
DENG Shao-dong1， ZHANG Peng2， LIN Li2*， XIAO Feng-xia2， LIN Jing-ran2
(1.The Second School of Clinical Medicine， Guangdong Medical College， Dongguan 523808， China;
, 百拇医药
2. College of Chinese Materia Medica， Guangzhou University of Traditional Chinese Medicine， Guangzhou 510006， China)
[Abstract]To study the in situ intestinal absorption of five oligosaccharides contained in Morinda officinalis How. (sucrose， kestose， nystose， 1F-Fructofuranosyinystose and Bajijiasu). The absorption of the five oligosaccharides in small intestine (duodenum， jejunum and ileum) and colon of rats and their contents were investigated by using in situ single-pass perfusion model and HPLC-ELSD. The effects of drug concentration， pH in perfusate and P-glycoprotein inhibitor on the intestinal absorption were investigated to define the intestinal absorption mechanism of the five oligosaccharides in rats. According to the results， all of the five oligosaccharides were absorbed in the whole intestine， and their absorption rates were affected by the pH of the perfusion solution， drug concentration and intestinal segments. Verapamil Hydrochloride could significantly increase the absorptive amount of sucrose and Bajijiasu， suggesting sucrose and Bajijiasu are P-gp′s substrate. The five oligosaccharides are absorbed mainly through passive diffusion in the intestinal segments， without saturated absorption. They are absorbed well in all intestines and mainly in duodenum and jejunum.
, 百拇医药
[Key words]oligosaccharide extracted from Morinda officinalis; intestinal absorption; single-pass intestinal perfusion; P-glycoprotein
doi：10.4268/cjcmm20150126
巴戟天为茜草科植物巴戟天Morinda officinalis How. 的肉质根，归肾、肝经，具有补肾助阳之功效，自古被誉为“补肾阳之要药”，已证实巴戟天糖类物质含量近50%，其中以低聚糖类成分为主[1]。近期药效研究表明，巴戟天低聚糖(oligosaccharide extracted from Morinda officinalis，OMO)可显著提高拟痴呆大鼠的学习记忆能力[2]、改善痴呆症状[3]，其中巴戟甲素、耐斯糖等低聚糖单体活性成分也显示具有神经细胞保护作用[4]、抗抑郁[5]、抗骨质疏松[6]等多种生物活性，表明巴戟天低聚糖类成分具有显著的开发利用前景。目前，以巴戟天为原料开发出的药品均以口服剂型为主，如巴戟天寡糖胶囊、巴戟口服液等，然而关于巴戟天低聚糖的胃肠道吸收机制研究的报道较少。因此，本研究采用大鼠在体肠单向灌流模型考察该巴戟天低聚糖有效部位中蔗糖、蔗果三糖、耐斯糖、1F-果呋喃糖基耐斯糖和巴戟甲素等5种低聚糖类成分的大鼠肠吸收特点，以揭示巴戟天低聚糖类成分的肠道吸收机制，确定各成分的最佳吸收部位，并考察了P-gp对巴戟天低聚糖类成分吸收的影响，以期为巴戟天低聚糖类药物的剂型开发及其在临床上的合理用药提供科学依据。, 百拇医药(邓少东 张鹏 林励 肖凤霞 林靖然)