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基于外翻肠囊模型考察人参、生姜单煎及合煎液纳米相态的肠吸收特性差异 被引量:1

Differences in Intestinal Absorption Characteristics of Nanophase in Single and Combined Decoctions of Ginseng Radix et Rhizoma and Zingiberis Rhizoma Recens Based on Everted Gut Sac Model
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摘要 目的:比较人参、生姜单煎和配伍合煎形成的纳米相态(NP)在大鼠肠吸收差异,探讨人参生姜合煎后形成的新NP对人参、生姜主要成分吸收的影响。方法:采用差速离心和透析技术分别富集人参、生姜单煎与合煎液中的NP;采用透射电子显微镜、粒度分析仪、纳米颗粒跟踪分析仪对其形态、粒径、Zeta电位、浓度等进行表征;采用外翻肠囊模型,以超高效液相色谱-三重四极杆串联质谱法(UPLC-QqQ-MS/MS)对人参、生姜单煎、合煎的NP肠吸收液中指标性成分进行分析,以单位面积实际累积吸收量(Q实际)、吸收速率常数(Ka)、表观渗透系数(Papp)为评价指标,考察上述NP在十二指肠、空肠、回肠、结肠中的吸收特性。结果:人参、生姜单煎液与合煎液中均存在不规则球形NP,且合煎形成的NP中成分含量多低于单煎NP。其中,10种成分可吸收进入肠囊,主要吸收部位在小肠,Papp均>1×10^(-5)cm·min^(-1)。与单煎液NP比较,人参皂苷Rb1、人参皂苷Rf、4-姜酚、6-姜烯酚等成分的Q实际及Ka在合煎液NP中显著升高,而人参皂苷Re、6-姜酚则显著降低(P<0.01);除人参皂苷Re、人参皂苷Rd外,其余成分的Papp在合煎液NP中均显著升高(P<0.01)。此外,人参皂苷Rb1、人参皂苷Rd、人参皂苷Ro的Q实际最大肠段部位前移,人参皂苷Rg1、人参皂苷Re、8-姜酚后移;人参皂苷Rb1、人参皂苷Rg1、人参皂苷Rd、人参皂苷Ro的Ka最大肠段部位及Papp最大肠段部位前移,人参皂苷Re、4-姜酚则后移。结论:人参、生姜合煎有助于促进二者有效成分的吸收,同时改变部分肠段对有效成分的吸收行为,该研究可为后续二药配伍机制研究提供参考。 Objective:To compare the differences in intestinal absorption of nanophase(NP)formed by single decoction and combined decoction of Ginseng Radix et Rhizoma(GRR)and Zingiberis Rhizoma Recens(ZRR)in rats,and to investigate the effects of new NP formed by the combined decoction on the absorption of main components in GRR and ZRR.Method:Differential centrifugation and dialysis techniques were used to enrich NP in the single and combined decoctions of GRR and ZRR,respectively.The microstructure,particle size,Zeta potential and concentration of the NP were analyzed by transmission electron microscope,particle size analyzer and nanoparticle tracking analyzer.Based on everted gut sac model,the index components in the intestinal absorption solution of NP from the single and combined decoctions were analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS).The per unit area actual value of cumulative intestinal absorption(Qactual),absorption rate constan(t Ka)and apparent permeability coefficient(Papp)were used as the evaluating indexes to investigate the absorption characteristics of the aforementioned NP in the duodenum,jejunum,ileum and colon.Result:Irregularly spherical NP was present in the single and combined decoctions,and the contents of components in NP of the combined decoction were mostly lower than those in the single decoction.In these NP,ten components could be absorbed into the intestinal sac,with the main absorption site being the small intestine,and the Papp was greater than 1×10^(-5) cm·min^(-1).Compared with NP in the single decoction,the Qactual and Ka of ginsenoside Rb1,ginsenoside Rf,4-gingerol and 6-shogaol were significantly increased in NP of the combined decoction,while ginsenoside Re and 6-gingerol were significantly decreased(P<0.01).Except for ginsenoside Re and ginsenoside Rd,the Papp of the remaining constituents was significantly increased in NP of the combined decoction(P<0.01).In addition,the maximum intestinal segment site of Qactual was shifted forward for ginsenoside Rb1,ginsenoside Rd and ginsenoside Ro,while shifted backward for ginsenoside Rg1,ginsenoside Re and 8-gingerol.The maximal intestinal segment sites of Ka and Papp of ginsenoside Rb1,ginsenoside Rg1,ginsenoside Rd and ginsenoside Ro shifted forward,while ginsenoside Re and 4-gingerol were shifted backward.Conclusion:The combined decoction of GRR and ZRR is helpful to promote the absorption of the effective components of the two,and changes the absorption behavior of the effective components in some intestinal segments.This study provides a reference for the subsequent research on the compatibility mechanism of the two medicines.
作者 郭小萌 王琪 李美景 张楠 龚慕辛 GUO Xiaomeng;WANG Qi;LI Meijing;ZHANG Nan;GONG Muxin(Beijing Key Laboratory of Traditional Chinese Medicine(TCM)Collateral Disease Theory Research,School of TCM,Capital Medical University,Beijing 100069,China)
出处 《中国实验方剂学杂志》 CAS CSCD 北大核心 2024年第22期231-242,共12页 Chinese Journal of Experimental Traditional Medical Formulae
基金 国家自然科学基金项目(81473360)。
关键词 人参 生姜 结构中药学 外翻肠囊 纳米相态 中药配伍 肠吸收 Ginseng Radix et Rhizoma Zingiberis Rhizoma Recens structural Chinese medicine everted intestinal sac nanophase Chinese medicine compatibility intestinal absorption
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