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丹参素对OATP1B1摄取瑞舒伐他汀的影响及其机制研究-药理学专业论文
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摘要
4.以 OATPIBI 强抑制剂四溴酚酞磺酸钠(BSP)为探针平行对照实验,结
果显示,BSP 抑制瑞舒伐他汀摄取的抑制参数 TC50=I7.92μM,而丹参素的抑制 参数 TC50=58.55μM。丹参素抑制 HepG2 细胞摄取瑞舒伐他汀的能力弱于 BSP。
结论:
I.丹参素能诱导 HepG2 细胞 SLCOIBI mRNA 及 OATPIBI 的表达,并且能 够增加 OATPIBI 的转运摄取能力。
2.当丹参素诱导 OATPIBI 表达时间短﹑浓度较低时,丹参素对 OATPIBI
摄取瑞舒伐他汀表现为抑制作用;当诱导时间延长及浓度加大时,其对 OATPIBI
摄取瑞舒伐他汀表现为诱导作用。
关键词:丹参素;瑞舒伐他汀;HepG2 细胞;OATPIBI
Abs
Abstract
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ABSTRACT
Background:
Danshensu( salvianic acid A) is a phenolic aromatic acid compound isolated from salvia miltiorrhiza. The prophase researches of our research group show that danshensu is the substrate of organic anion transporting polypeptide IBI or the homologous transporter of rat oatplb2.Rosuvastatin is also the substrate of OATPIBI
/ oatplb2,danshensu and rosuvastatin are often used together in clinical practice, whether danshensu show the competitive inhibition on the transport and uptake of rosuvastatin by OATPIBI,and then weaken the lipid-lowering efficacy of rosuvastatin after decreasing the drug concentration of targets? However, that was not the case of clinical effect,the reason is paid more attention to!So this topic will carry out the study around the influence of the SLCOIBImRNA which is the coding genes of transporter OATPIBI and the function expression of OATPIBI protein caused by danshensu,Tt will provide theoretical and experimental basis on lipid lowering therapy to use danshensu and rosuvastatin together.
Objectives:
Based on the successfully constructed HepG2 cell model with high expression of SLCOIBI mRNA and OATPIBI,we explored the influence of danshensu on the transcription of SLCOIBI gene and the expression of OATPIBI by RT-PCR and Western-blot.LC-MS is used to study the influence caused by danshensu on the uptake of rosuvastatin by OATPIBI,To clarify the effect and mechanism of danshensu on the uptake of rosuvastatin by OATPIBI.
Methods:
I. Cultivate HepG2 cells regularly, Observe the shape and status of cells and draw the cell growth curve.
Test the toxicity of danshensu,rifampicin
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