目的 研究多药耐药相关蛋白2（multidrug resistance protein 2，MRP2）对汉黄芩素及其主要II相代谢产物药动学特征的影响。方法 FVB野生型和MRP2^-/-小鼠ig汉黄芩素β-环糊精包合物后，于不同时间点眼眶取血。采用超高效液相色谱-质谱联用技术检测汉黄芩素、汉黄芩苷、汉黄芩素-7-O-硫酸酯的血药浓度，采用DAS 2.0软件以非房室模型计算药动学参数。结果 3个成分的线性关系良好，准确度、精密度、稳定性、回收率等符合要求。汉黄芩素主要以II相代谢产物汉黄芩苷和汉黄芩素-7-O-硫酸酯存在，均在30 min内达到最大血药浓度。汉黄芩苷的达峰浓度（C_max）和药时曲线下面积（AUC_0~t）最高，汉黄芩素-7-O-硫酸酯次之，汉黄芩素最低。与FVB野生型组比较，MRP2^-/-组汉黄芩苷和汉黄芩素-7-O-硫酸酯的C_max和AUC_0~t显著增加（P<0.05、0.01）。结论 MRP2介导了汉黄芩苷和汉黄芩素-7-O-硫酸酯的外排过程，显著影响汉黄芩素的体内处置过程。

Objective To study the effect of multidrug resistance protein 2 (MRP2) on pharmacokinetic behaviors of wogonin and its major phase Ⅱ metabolites. Methods FVB wild-type and MRP2^−/− mice were taken blood from eye sockets at different time points after ig wogonin withβ-cyclodextrin. The plasma concentrations of wogonin, wogonoside and wogonin-7-O-sulfate were determined by ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) method. The pharmacokinetic parameters were calculated by non-compartmental models with DAS 2.0 software. Results The linearity of three components was good, and accuracy, precision, stability and recovery rate met the requirements. Wogonin was mostly biotransformed to wogonoside and wogonin-7-O-sulfate and these analytes reached peak concentration (C_max) within 30 min. The plasma C_maxandarea under the curve(AUC_0~t) of wogonoside were the highest, followed by wogonin-7-O-sulfate, and wogonin was the lowest. Compared with FVB wild-type group, C_max and AUC_0~t of wogonoside and wogonin-7-O-sulfate in MRP2^−/− group were significantly increased (P < 0.05, 0.01). Conclusion MRP2 mediated the efflux of wogonoside and wogonin-7-O-sulfate, significantly affected the disposal process of wogonin in vivo.

R285.61

国家自然科学基金资助项目（81560703）；湖北民族大学大学生创新创业训练计划项目（S202110517027）；广西大学高层次人才基金项目（A3370051006）；风湿性疾病发生与干预湖北省重点实验室（湖北民族大学）项目（PT022202）