基于寡肽转运蛋白的氟苯尼考肠吸收特性研究

doi:10.11843/j.issn.0366-6964.2023.03.035

摘要/Abstract

摘要： 本研究旨在考察氟苯尼考(florfenicol, FF)在不同浓度下的肠吸收特性，探究寡肽转运蛋白对氟苯尼考肠吸收的影响。采用高效液相色谱法测定灌流样品中氟苯尼考的含量，建立大鼠在体肠循环灌流模型，考察不同浓度药物对氟苯尼考吸收速率的影响；以寡肽转运蛋白1(oligopeptide transporter 1, PepT1)的典型底物甘氨酰肌氨酸来考察PepT1对氟苯尼考吸收的影响，计算氟苯尼考的药物吸收速率常数(K_a)及有效渗透系数(P_eff)。结果表明，所建立的FF含量测定方法准确度、精密度均符合检测要求。FF低(50 μg·mL^-1)、中(75 μg·mL^-1)、高(100 μg·mL^-1)3个浓度下的K_a(μg·h^-1·cm^-2)值分别为1.48±0.02、1.73±0.14、1.90±0.07，低浓度与中高浓度组间均具有显著性差异(P＜0.05)；有效渗透系数P_eff(×10² cm·h^-1)分别为84.12±2.40、101.28±4.57、110.64±5.70，3个组别均具有显著性差异(P＜0.05)，FF跨肠道吸收的K_a与P_eff在试验所用浓度范围内随浓度增加而增加。添加高浓度(100 μg·mL^-1)甘氨酰肌氨酸(GlySar)后，P_eff(×10² cm·h^-1)值为97.2±5.30，与未添加组相比具有显著性差异，加入PepT1典型底物后，氟苯尼考的吸收显著性下降。结果说明，氟苯尼考的吸收方式不是只有简单扩散，PepT1可能作为主动转运蛋白参与了氟苯尼考的跨肠道吸收过程。

关键词: 氟苯尼考, 肠道吸收, 大鼠在体肠循环灌流, 寡肽转运蛋白

Abstract: The aim of this study was to investigate the intestinal absorption characteristics of florfenicol (FF) at different concentrations, and to explore the effect of oligopeptide transporter on intestinal absorption of florfenicol. The content of florfenicol in the perfusion samples was determined by high performance liquid chromatography (HPLC), and the in vivo circulation pass perfusion model was established to investigate the effect of different concentrations of drugs on the absorption rate of florfenicol; The effect of PepT1 on florfenicol uptake was investigated by the typical substrate of oligopeptide transporter 1 (PepT1), glycine sarcosine, and the drug absorption rate constant (K_a) and effective permeability coefficient (P_eff) of florfenicol were calculated. he results show that the accuracy and precision of the established method for determination of FF content meet the detection requirements. The K_a (μg·h^-1·cm^-2) values at low (50 μg·mL^-1), medium (75 μg·mL^-1) and high (100 μg·mL^-1) concentrations were 1.48±0.02, 1.73±0.14 and 1.90±0.07, respectively, and there were significant differences between low and medium concentration groups (P<0.05). The effective permeability coefficient P_eff (×10² cm·h^-1) was 84.12±2.40, 101.28±4.57, 110.64±5.70, respectively, with significant differences among the three groups (P<0.05). The K_a and P_eff absorbed by FF across the gut increased with increasing concentration in the concentration range used in the experiment. The P_eff (×10² cm·h^-1) value was 97.2±5.30 after the addition of high concentration (100 μg·mL^-1) glycine sarcosine (GlySar), which was significantly different from that of the non-addition group. The absorption of florfenicol decreased significantly after the addition of PepT1 typical substrate. The above experimental results suggest that the absorption mechanism of florfenicol is not only simple diffusion, and PepT1 as an active transporter participates in the trans-intestinal absorption process of florfenicol.

Key words: florfenicol, intestinal absorption, in vivo circulation pass perfusion model, oligopeptide transporters

中图分类号:

S859.796

陈洋, 王悦力, 陈诗奇, 李楠鑫, 张伟, 舒刚, 徐傅能, 李昊欢, 林居纯, 符华林. 基于寡肽转运蛋白的氟苯尼考肠吸收特性研究[J]. 畜牧兽医学报, 2023, 54(3): 1240-1248.

CHEN Yang, WANG Yueli, CHEN Shiqi, LI Nanxin, ZHANG Wei, SHU Gang, XU Funeng, LI Haohuan, LIN Juchun, FU Hualin. Intestinal Absorption Characteristics of Florfenicol based on Oligopeptide Transporters[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(3): 1240-1248.

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