枸杞多糖对大鼠CYP450酶的调控作用

doi:10.3969/j.issn.2095-9400.2020.03.011

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摘要目的：评价枸杞多糖对大鼠肝细胞色素P450（CYP450）酶活力和基因表达的调控作用。方法：SD大鼠随机分为实验组（低剂量组、高剂量组）和对照组，分别给予低高剂量（250、500 mg/kg）枸杞多糖和纯化水2周，于第15天同时给予4种探针药（非那西丁、安非他酮、甲苯磺丁脲、咪达唑仑）的混合溶液，测定给药后不同时间点探针药的浓度并计算药动学参数，推测相关CYP450酶活力变化。RT-PCR法用于观测CYP450的基因表达变化。结果：与对照组相比，高剂量组大鼠甲苯磺丁脲药动学参数CLz/F降低27%，AUC(0-t)和Cmax分别增加50%和28%；低剂量组大鼠咪达唑仑CLz/F和Vz/F分别降低了25%和35%，AUC(0-t)增加了38%；高剂量组大鼠咪达唑仑的CLz/F和Vz/F分别降低了34%和38%，AUC(0-t)、Tmax和Cmax分别增加了51%、50%和65%（P＜0.05）；非那西丁和安非他酮药动学参数差异无统计学意义（P＞0.05）。RT-PCR检测发现，与对照组比较，枸杞多糖能显著下调大鼠CYP2C11（高剂量组）、CYP3A1（低剂量组）和CYP3A1（高剂量组）mRNA水平，分别为56%、44%和68%，而对CYP1A2和CYP2B1没有影响。结论：枸杞多糖会降低CYP2C11和CYP3A1酶活力及mRNA表达水平。

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	黄爱芳
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	周子晔

关键词 ：枸杞多糖, CYP450, 活力, mRNA表达, 调控作用, 大鼠

Abstract：Objective: To evaluate the regulating effect of LyciumBarbarum polysaccharides (LBP) on activities and mRNA expressions of cytochrome P450 (CYP450) in rats. Methods: SD rats were randomly divided as test group (low-dose group, high-dose group) and control group. Treated with LBP and given pure water respectively for 14 days, the test group and control group were simultaneously given the mixture of four probes on day 15. Plasma concentration of probes was determined at a series of time-points after dosing. The activities of CYP450 were evaluated according to the pharmacokinetic parameters of corresponding probes. Real-time PCR was applied to assess the mRNA levels of CYP450. Results: Compared with control group, CLz/F of tolbutamide in high dose group rats decreased by 27%, AUC(0-t) and Cmax increased by 50% and 28%; CLz/F and Vz/F of midazolam in low dose group rats decreased by 25% and 35%, AUC(0-t) increased by 38%; CLz/F and Vz/F of midazolam inhigh dose group rats decreased by 34% and 38%, while AUC(0-t), Tmax and Cmax increased by 51%, 50% and 65%, respectively. In addition, treatment with LBP significantly down-regulated the mRNA expressions of CYP2C11 in high dose group and CYP3A1 in both low and high dose groups by 56%, 44% and 68% respectively. LBP had no impact on pharmacokinetics of phenacetin, bupropion and mRNA expressions of CYP1A2, CYP2B1. Conclusion: LBP can down-regulate the activities and mRNA expressions of CYP2C11 and CYP3A1.

Key words： LyciumBarbarum polysaccharides CYP450 activity mRNA expression modulation rats

基金资助:温州市科技计划项目（Y20160528）。

通讯作者: 周子晔，副主任药师，Email：redd88@163.com

作者简介: 黄爱芳（1966-），女，浙江温州人，副主任药师。

链接本文:

https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2020.03.011 或 https://xb.wmu.edu.cn/CN/Y2020/V50/I3/221

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