目的 对菟丝子-枸杞子药对中8种活性成分在早发性卵巢功能不全（premature ovarian insufficiency，POI）大鼠体内吸收特征进行分析，为菟丝子-枸杞子药对体内吸收机制的深入研究奠定基础。方法 基于UPLC-MS技术，采用在体单向肠灌流法对菟丝子-枸杞子药对中活性成分在POI大鼠体内不同肠段的吸收特征进行分析，分别考察不同药物质量浓度、肠壁吸附作用、P-糖蛋白（P-glycoprotein，P-gp）抑制剂、能量抑制剂对吸收的影响。结果 菟丝子-枸杞子药对灌流液质量浓度为0.1～0.4 g/mL时，金丝桃苷、异槲皮苷、阿魏酸、紫云英苷、槲皮素、山柰酚、异鼠李素7种成分在大鼠全肠段的吸收速率常数（K_a）和表观吸收系数（P_eff）无显著差异，表明这7种成分的吸收不存在自身质量浓度抑制，它们可能以被动扩散方式进入体循环，甜菜碱低质量浓度组K_a和P_eff与中、高质量浓度组存在显著差异（P＜0.01），中质量浓度组K_a和P_eff与高质量浓度组无显著差异，表明甜菜碱的吸收存在自身质量浓度抑制，其可能以主动转运方式进入体循环；肠壁对这些成分均无明显物理吸附作用；甜菜碱、金丝桃苷、异槲皮苷、阿魏酸、山柰酚吸收部位主要在十二指肠和空肠，紫云英苷、异鼠李素的吸收部位主要在十二指肠和回肠，槲皮素的吸收部位主要在回肠和空肠。P-gp抑制剂（维拉帕米）对甜菜碱、阿魏酸、槲皮素、山柰酚、异鼠李素5种成分的K_a和P_eff值有显著性影响（P＜0.05），可能为P-gp底物。能量抑制剂（2,4二硝基酚）对甜菜碱的K_a和P_eff值有显著性影响（P＜0.05），除此以外，对其他成分的K_a和P_eff值无显著性影响。结论 上述成分除甜菜碱外，其余成分在肠道中均吸收较差，推测可能与肠道菌群参与的化学成分代谢和中药引起的菌群内源性代谢有关。

Objective To analyze the in vivo absorption characteristics of eight active components of Tusizi (Cuscutae Semen)-Gouqizi (Lycii Fructus) herb pair in rats with premature ovarian insufficiency (POI), which laid the foundation for further study on the absorption mechanism of Cuscutae Semen-Lycii Fructus herb pair. Methods Based on UPLC-MS technology, the absorption characteristics of components of Cuscutae Semen-Lycii Fructus herb pair in different intestinal segments of POI rats were analyzed using unidirectional intestinal perfusion, and the effects of different Cuscutae Semen-Lycii Fructus herb pair concentrations, intestinal wall physisorption, P-glycoprotein (P-gp) inhibitor and energy inhibitor on absorption were investigated respectively. Results No significant differences in K_a and P_eff of the seven components (hyperoside, isoquercitrin, ferulic acid, astragalin, quercetin, kaempferol, and isorhamnetin) at concentrations of Cuscutae Semen-Lycii Fructus herb pair perfusion solution ranging from 0.1 to 0.4 g/mL in the whole intestinal segments of the rats. This suggests that the absorption of these seven components is not inhibited by their own mass concentration and that they may enter the body circulation by passive diffusion. A significant difference was observed between K_a and P_eff in the low concentration group of betaine compared to the medium and high concentration groups (P < 0.01), with no significant difference between K_a and P_eff in the medium concentration group and those in the high concentration group. This indicated that uptake of betaine may be inhibited by its own mass concentration and that it may enter the systemic circulation in the form of active transport. There was no significant physisorption of any of these components by the intestinal wall. The absorption sites for betaine, hyperoside, isoquercitrin, ferulic acid and kaempferol were primarily in the duodenum and jejunum, while the absorption sites of astragalin and isorhamnetin were mainly in the duodenum and ileum, and quercetin was mainly absorbed in the ileum and jejunum. The P-gp inhibitor (verapamil) significantly affected K_a and P_eff values for betaine, ferulic acid, quercetin, kaempferol and isorhamnetin (P < 0.05), suggesting that these components may be P-gp substrates. The energy inhibitor (2,4-dinitrophenol) significantly affected the K_a and P_eff values of betaine (P < 0.05), but did not have a significant effect on the K_a and P_eff values of the other components.Conclusion All ingredients, except betaine, were poorly absorbed in the intestine. This may be related to the metabolism of these chemical components in the gut microbiota and the endogenous metabolism of the flora induced by traditional Chinese medicine.

R285.5

黑龙江省重点研发计划项目（2022ZX02C08）；龙江科技英才春雁支持计划项目（CYCX24009）；黑龙江省双一流学科协同创新成果项目（LJGXCG2023-023）