外翻肠囊法研究肝豆汤醇提物主要成分的肠吸收特征(1)
[摘要] 为了探究复方肝豆汤醇提物中主要化学成分的肠吸收特性，该文采用大鼠外翻肠囊模型，选择肝豆汤醇提物中盐酸小檗碱、槲皮素、山柰素、大黄酸、大黄酚、芦荟大黄素6种主要成分作为考察对象，评价各成分在不同肠段的吸收特征。结果表明，肝豆汤醇提物中6种成分均可进入肠囊，在高、中、低3种不同质量浓度的肝豆汤醇提物中，盐酸小檗碱、槲皮素、山柰素3种成分在不同肠段的吸收均为线性吸收，符合零级吸收速率，且在空肠与回肠中吸收速率常数Ka随着剂量增加均增加(P<0.05)，符合被动吸收；而大黄酸在空肠和回肠中的Ka随着剂量增加并无显著性差异，符合主动转运。大黄酚和芦荟大黄素2种成分在肠段中吸收均较差。提示肠囊对肝豆汤醇提物中药物成分吸收具有选择性，各成分在肠囊中的吸收特征并不完全相同。
[关键词] 肝豆汤醇提物；多组分；外翻肠囊法；吸收速率常数
[Abstract] To study the intestinal absorptive characteristics of the ethanol extracts from Gandou decoction(GDD)， everted intestinal sac models were used. The six representative ingredients (berberine hydrochloride， quercetin， kaempferide， rhein， chrysophanol， and aloe emodin) of GDD， were selected as the experimental targets to investigate the absorptive characteristics of various ingredients in different intestinal sections. The results showed that all six ingredients from GDD were detected in the intestinal sac， three active ingredients (berberine hydrochloride， quercetin， kaempferide) in high， medium and low doses had linear absorption properties in the small intestine segment， consistent with zero-order absorption rate；in addition， the absorption rate constant (Ka) of three components in jejunum and ileum were increased with the increase of the concentration of GDD (P<0.05)， consistent with passive absorption. However， the Ka of rhein in jejunum and ileum showed little difference with the increase of dosage， suggesting a possibility of active transport mechanism. Chrysophanol and aloe-emodin were poorly absorbed in the two segments， which had not been detected in the previous time. The results suggested that the components of GDD were selectively absorbed in the intestinal sac， and the absorption characteristic of the ingredients were not exactly similar.
, 百拇医药
[Key words] ethanol extracts of Gandou decoction；multi-component；everted intestinal sac； Ka
肝豆湯用于治疗肝豆状核变性(hepatolenticular degeneration， HLD)已有40年历史，具有清热解毒，利尿通淋，活血化瘀的功效，临床疗效确切[1-2]，2008年被《肝豆状核变性诊断与治疗指南》推荐为常规治疗HLD基本方[3-4]。前期研究表明，肝豆汤含药血清具有显著的细胞内排铜作用，能够通过多靶点、多途径调控铜代谢通路达到细胞内排铜效果[5]。
肝豆汤由大黄、黄连、姜黄、金钱草、泽泻、三七6味药组方而成，成分复杂，药效物质基础尚不明确，限制了其质量控制及开发应用。通常认为中药及其复方口服给药后只有经胃肠吸收入血，通过血液循环才能够发挥药效作用。为了明确肝豆方中主要成分的肠吸收特性，本研究选取肝豆汤中具有代表性的蒽醌、黄酮和生物碱3类成分为考察对象，建立方中盐酸小檗碱、槲皮素、山柰素、大黄酸、大黄酚和芦荟大黄素6种成分的超高效液相色谱(UPLC)检测方法，通过外翻肠囊模型研究肝豆汤醇提物中6种化学成分的肠吸收特征，为肝豆汤药效物质基础的研究奠定基础。
1 材料
1.1 仪器
Agelent 1290超高效液相色谱仪(美国安捷伦公司)；电热恒温水浴箱(上海跃进医疗器械厂)；混合气瓶：95% O2，5% CO2(合肥公益化工产品有限责任公司)；麦氏浴槽；CP225D型1/10万电子天平(德国Sartorius公司)；Eppendorf AG 5401高速冷冻离心机(德国Eppendorf公司)；KQ-100E型超声波清洗器(昆山市超声仪器有限公司)。, 百拇医药(刘艺 程梅梅 董健健 周安)
[关键词] 肝豆汤醇提物；多组分；外翻肠囊法；吸收速率常数
[Abstract] To study the intestinal absorptive characteristics of the ethanol extracts from Gandou decoction(GDD)， everted intestinal sac models were used. The six representative ingredients (berberine hydrochloride， quercetin， kaempferide， rhein， chrysophanol， and aloe emodin) of GDD， were selected as the experimental targets to investigate the absorptive characteristics of various ingredients in different intestinal sections. The results showed that all six ingredients from GDD were detected in the intestinal sac， three active ingredients (berberine hydrochloride， quercetin， kaempferide) in high， medium and low doses had linear absorption properties in the small intestine segment， consistent with zero-order absorption rate；in addition， the absorption rate constant (Ka) of three components in jejunum and ileum were increased with the increase of the concentration of GDD (P<0.05)， consistent with passive absorption. However， the Ka of rhein in jejunum and ileum showed little difference with the increase of dosage， suggesting a possibility of active transport mechanism. Chrysophanol and aloe-emodin were poorly absorbed in the two segments， which had not been detected in the previous time. The results suggested that the components of GDD were selectively absorbed in the intestinal sac， and the absorption characteristic of the ingredients were not exactly similar.
, 百拇医药
[Key words] ethanol extracts of Gandou decoction；multi-component；everted intestinal sac； Ka
肝豆湯用于治疗肝豆状核变性(hepatolenticular degeneration， HLD)已有40年历史，具有清热解毒，利尿通淋，活血化瘀的功效，临床疗效确切[1-2]，2008年被《肝豆状核变性诊断与治疗指南》推荐为常规治疗HLD基本方[3-4]。前期研究表明，肝豆汤含药血清具有显著的细胞内排铜作用，能够通过多靶点、多途径调控铜代谢通路达到细胞内排铜效果[5]。
肝豆汤由大黄、黄连、姜黄、金钱草、泽泻、三七6味药组方而成，成分复杂，药效物质基础尚不明确，限制了其质量控制及开发应用。通常认为中药及其复方口服给药后只有经胃肠吸收入血，通过血液循环才能够发挥药效作用。为了明确肝豆方中主要成分的肠吸收特性，本研究选取肝豆汤中具有代表性的蒽醌、黄酮和生物碱3类成分为考察对象，建立方中盐酸小檗碱、槲皮素、山柰素、大黄酸、大黄酚和芦荟大黄素6种成分的超高效液相色谱(UPLC)检测方法，通过外翻肠囊模型研究肝豆汤醇提物中6种化学成分的肠吸收特征，为肝豆汤药效物质基础的研究奠定基础。
1 材料
1.1 仪器
Agelent 1290超高效液相色谱仪(美国安捷伦公司)；电热恒温水浴箱(上海跃进医疗器械厂)；混合气瓶：95% O2，5% CO2(合肥公益化工产品有限责任公司)；麦氏浴槽；CP225D型1/10万电子天平(德国Sartorius公司)；Eppendorf AG 5401高速冷冻离心机(德国Eppendorf公司)；KQ-100E型超声波清洗器(昆山市超声仪器有限公司)。, 百拇医药(刘艺 程梅梅 董健健 周安)