Transport of salvianolic acid B via the human organic anion transporter 1B1 in the liver
Transport of salvianolic acid B via the human organic anion transporter 1B1 in the liver
复制标题
丹酚酸 B 通过肝脏中的人体有机阴离子转运蛋白 1B1 转运
DOI：
10.1002/ptr.6216
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发表时间：
2019-01-01
影响因子：
7.2
通讯作者：
Wen, Jinhua
中科院分区：
文献类型：
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作者：
Cao, Li;Zhou, Jian;Wen, Jinhua
丹酚酸B （Salvianolic acid B， SAB）在肝脏中浓度较高，但其在肝脏中的分布机制尚不清楚。本研究的目的是探讨SAB的肝脏摄取机制。在本研究中，我们首先探讨了SAB在HepG2细胞中的摄取特征以及利福平对摄取的影响。然后，我们探讨了SAB对HepG2细胞摄取匹伐他汀的影响。最后，我们建立HEK239T‐OATP1B1细胞模型来证实OATP1B1是否介导了SAB的转运。结果表明，SAB在HepG2细胞中的摄取动力学参数Vmax和Km分别为21.28±2.06 pmol mg−1 / protein min−1和28.47±7.36 μM。利福平抑制HepG2细胞对SAB的摄取（IC50为5.85±1.70 μM）， SAB影响HepG2细胞对匹伐他汀的摄取（IC50为27.67±1.90 μM）。HEK239T‐OATP1B1细胞对SAB的摄取动力学参数Vmax和Km分别为60.03±6.16 pmol mg - 1 /蛋白min - 1和87.24±15.28 μM，而EGFP‐HEK293细胞对SAB的摄取动力学参数Vmax和Km分别为14.04±2.53 pmol mg - 1 /蛋白min - 1和56.53±15.50 μM。SAB对HEK239T - OATP1B1细胞中OATP1B1的表达没有影响。综上所述，本研究表明OATP1B1参与SAB在肝脏中的运输和积累。
Salvianolic acid B (SAB) has a high concentration in the liver, but the mechanism of its distribution in the liver is unclear. The aim of this study was to investigate the mechanisms of hepatic uptake of SAB. In this study, we first explored the uptake features of SAB in HepG2 cells and the effect of rifampicin on uptake. Then, we explored the effects of SAB on the uptake of pitavastatin in HepG2 cells. Finally, we established an HEK239T‐OATP1B1 cell model to confirm whether OATP1B1 mediated the transport of SAB. Results showed that the uptake kinetic parameters Vmax and Km for SAB in HepG2 cells were 21.28 ± 2.06 pmol mg−1 per protein min−1 and 28.47 ± 7.36 μM, respectively. Rifampicin inhibited the uptake of SAB in HepG2 cells (IC50 was 5.85 ± 1.70 μM), and SAB affected the uptake of pitavastatin in HepG2 cells (IC50 was 27.67 ± 1.90 μM). The uptake kinetic parameters Vmax and Km for SAB in HEK239T‐OATP1B1 were 60.03 ± 6.16 pmol mg−1 per protein min−1 and 87.24 ± 15.28 μM, respectively, whereas in EGFP‐HEK293 cells were 14.04 ± 2.53 pmol mg−1 per protein min−1 and 56.53 ± 15.50 μM. The SAB had no effect of on the expression of OATP1B1 in HEK239T‐OATP1B1 cells. In conclusion, this study demonstrated that OATP1B1 contributes to the transport and accumulation of SAB in the liver.