9种注射用辅料对肝脏有机阴离子转运多肽OATP1B1和OATP1B3的影响  

Effects of nine injective excipients on liver organic anion-transporting polypeptides OATP1B1 and OATP1B3

作　　者：肖雨蒙 李亚飞 蒋学华[1] 王凌[1] XIAO Yumeng;LI Yafei;JIANG Xuehua;WANG Ling(West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China)

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《华西药学杂志》2023年第2期151-156,共6页West China Journal of Pharmaceutical Sciences

摘　　要：目的研究9种注射用辅料对HepG2细胞上OATP1B1和OATP1B3转运体的影响。方法采用噻唑蓝法考察9种注射用辅料对HepG2细胞存活率的影响;实时荧光聚合酶链反应法以及蛋白质印迹法测定辅料对HepG2细胞中OATP1B1和OATP1B3 mRNA及蛋白表达量的影响;以匹伐他汀作为探针底物,用LC-MS/MS法检测细胞摄取实验中匹伐他汀的胞内蓄积量。结果Tween80和大豆油能显著性下调HepG2细胞内OATP1B1 mRNA和蛋白表达,甘露醇仅能下调OATP1B1 mRNA的表达量而对蛋白表达无影响;Tween20、Tween80、蔗糖、PEG600和PEG4000能显著下调HepG2细胞内OATP1B3 mRNA和蛋白的表达;PEG600和PEG4000能显著降低HepG2细胞内匹伐他汀的蓄积量。结论PEG600和PEG4000能通过抑制OATP1B3mRNA和蛋白表达而减少匹伐他汀在HepG2细胞上的摄取量。OBJECTIVE To investigate the influence of injective excipients on OATP1B1 and OATP1B3 in HepG2 cells.METHODS MTT assay was used to investigate the effects of pharmaceutical injection excipients on the cell viability of HepG2 cells.The effects of injection excipients on the mRNA and protein levels of OATP1B1 and OATP1B3 in HepG2 cells were detected by qPCRand Western blot.Pitavastatin was used as the probe substrate to detect the intracellular accumulation in the cell uptake experiment by HPLC-MS/MS.RESULTS Tween80 and soybean oil significantly decreased the expression of OATP1B1 mRNA and protein in HepG2 cells,while mannitol only decreased the mRNA expression without affecting protein expression of OATP1B1.Tween20,Tween80,sucrose,PEG600 and PEG4000 significantly inhibit the expression of OATP1B3 mRNA and protein in HepG2 cells.PEG600 and PEG4000 significantly reduced the accumulation of Pitavastatin in HepG2 cells.CONCLUSION PEG600 and PEG4000 reduce the uptake of Pitavastatin in HepG2 cells by inhibiting the expressions of OATP1B3 mRNA and protein.

关 键 词：注射用辅料 肝脏 有机阴离子转运多肽 噻唑蓝法 OATP1B1 OATP1B3 HEPG2 匹伐他汀 

分 类 号：R96[医药卫生—药理学]