中国中药杂志

2021, v.46(01) 196-205

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基于外翻肠囊模型研究荭草提取物在正常和心肌缺血模型大鼠中的肠吸收特征
Intestinal absorption characteristics of Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats via everted intestinal sac models

刘春花;王明金;杨淑婷;黎娜;陆苑;潘洁;李勇军;王永林;孙佳;
LIU Chun-hua;WANG Ming-jin;YANG Shu-ting;LI Na;LU Yuan;PAN Jie;LI Yong-jun;WANG Yong-lin;SUN Jia;State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and Traditional Chinese Medicine (Ministry of Education), Guizhou Medical University;Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University;School of Pharmacy, Guizhou Medical University;

摘要(Abstract):

采用大鼠外翻肠囊模型考察荭草提取物在正常和心肌缺血模型大鼠的肠吸收特征。收集荭草提取物(5.0,10.0,20.0 mg·mL(-1))在各肠段中的肠囊液,采用UPLC-TQD测定肠囊液中荭草素、异荭草素、牡荆素、原儿茶酸、山柰素-3-O-β-D-葡萄糖苷、槲皮苷6个化学成分的含量,计算吸收速率和累积吸收量,同时考察P-糖蛋白(P-gp)抑制剂对6种成分肠吸收的影响。结果发现,正常状态下,低、中、高浓度下,主要吸收部位分别是十二指肠、结肠和回肠;心肌缺血状态下,低浓度主要集中在回肠和空肠,中浓度在回肠,高浓度在十二指肠和回肠。与正常组相比,模型组中6种成分的吸收速率和累积吸收量均显著下降。P-gp抑制剂能显著提高模型组中6种成分的吸收速率和累积吸收量,推测荭草中的6种成分可能是P-gp的底物。外翻肠囊模型能有效评价荭草提取物中这6种成分在正常和心肌缺血状态下的肠吸收特征,该研究为荭草的临床用药和深入开发利用提供参考依据。
The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL(-1))在各肠段中的肠囊液,采用UPLC-TQD测定肠囊液中荭草素、异荭草素、牡荆素、原儿茶酸、山柰素-3-O-β-D-葡萄糖苷、槲皮苷6个化学成分的含量,计算吸收速率和累积吸收量,同时考察P-糖蛋白(P-gp)抑制剂对6种成分肠吸收的影响。结果发现,正常状态下,低、中、高浓度下,主要吸收部位分别是十二指肠、结肠和回肠;心肌缺血状态下,低浓度主要集中在回肠和空肠,中浓度在回肠,高浓度在十二指肠和回肠。与正常组相比,模型组中6种成分的吸收速率和累积吸收量均显著下降。P-gp抑制剂能显著提高模型组中6种成分的吸收速率和累积吸收量,推测荭草中的6种成分可能是P-gp的底物。外翻肠囊模型能有效评价荭草提取物中这6种成分在正常和心肌缺血状态下的肠吸收特征,该研究为荭草的临床用药和深入开发利用提供参考依据。
The present study is to investigate the absorption characteristics of the main components in Polygonum orientale extract in normal and isoproterenol-induced myocardial ischemia model rats with everted intestinal sac models. Intestinal sac fluid samples were collected in different part of intestine(duodenum, jejunum, ileum, colon) at different time after administration of different concentration of P. orientale extract(5.0,10.0, 20.0 mg·mL(-1)). An UPLC-TQD method was employed for the determination of six components including orientin, isoorientin, vitexin, protocatechuic acid, kaempferol-3-O-β-D-glucoside and quercitrin in the intestinal sac samples. The absorption rate and cumulative absorption were calculated to analyze the intestinal absorption characteristics of six components in normal and myocardial ischemia model rats. The P-glycoprotein(P-gp) inhibitor was applied to investigate influence of intestinal absorption of six components in P. orientale extract. The results showed that the main absorption sites were concentrated on the duodenum at low concentration, while they were the colon at the medium concentration and the ileum at high concentration in control groups. In the condition of myocardial ischemia model, the main absorption sites focus on the ileum and jejunum at low concentration; the main absorption sites were in the ileum at the medium concentration and main absorption sites were the duodenum and ileum at high concentration. Compared with the normal group, the absorption rate and cumulative absorption of the six components significantly decreased in the model group. P-gp inhibitor markedly increased the absorption rate and cumulative absorption of six components in the model group, inferring that the 6 components may be the substrates of P-gp, and the mechanism needs further study. In this study, it is revealed that the six components of P. orientale extract can be absorbed into the intestinal sac, and it is an effective method to assess the intestinal absorption characteristics of P. orientale extract through everted intestinal sac model, providing data support for the clinical application and further development of P. orientale.

关键词(KeyWords): 荭草提取物;肠吸收;离体外翻肠囊法;心肌缺血;P-糖蛋白抑制剂
Polygonum orientale extract;intestinal absorption;everted intestinal sac model;myocardial ischemia;P-gp inhibitor

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81660712,81803700,U1812403);; 贵州省自然科学基金项目(黔科合基础[2020]1Z068);; 贵州省科学技术厅项目(黔科合平台人才[2016]5613/5677,黔科合平台人才[2017]5718);; 贵州省中医药管理局中医药、民族医药科学技术研究项目(QZYY-2018-108);; 中央引导地方科技专项(黔科中引地[2018]4006)

作者(Authors): 刘春花;王明金;杨淑婷;黎娜;陆苑;潘洁;李勇军;王永林;孙佳;
LIU Chun-hua;WANG Ming-jin;YANG Shu-ting;LI Na;LU Yuan;PAN Jie;LI Yong-jun;WANG Yong-lin;SUN Jia;State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and Traditional Chinese Medicine (Ministry of Education), Guizhou Medical University;Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University;School of Pharmacy, Guizhou Medical University;

DOI: 10.19540/j.cnki.cjcmm.20201010.201

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