扶正化瘀方对原代大鼠肝细胞中CYP450的影响

张亚蕾; 郑天慧; 刘伟; 陶艳艳; 王长虹; 杨涛; 刘成海

doi:10.13422/j.cnki.syfjx.20180902

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扶正化瘀方对原代大鼠肝细胞中CYP450的影响

制药与工艺 | 更新时间：2024-01-04

- 扶正化瘀方对原代大鼠肝细胞中CYP450的影响
- Effect of Fuzheng Huayu Recipe on CYP450 in Primary Rat Hepatocytes
- 中国实验方剂学杂志 2018年24卷第9期页码：22-28
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家国际科技合作专项（2014DFA31440）;上海市医学领军人才计划项目（LJ10005）;上海中医药事业发展三年行动计划项目（ZY3-CCCX-2-1003）
- DOI：10.13422/j.cnki.syfjx.20180902
  中图分类号： R285.5
- 纸质出版日期：2018
- 稿件说明：
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张亚蕾, 郑天慧, 刘伟, 等. 扶正化瘀方对原代大鼠肝细胞中CYP450的影响[J]. 中国实验方剂学杂志, 2018,24(9):22-28.

ZHANG Ya-lei, ZHENG Tian-hui, LIU Wei, et al. Effect of Fuzheng Huayu Recipe on CYP450 in Primary Rat Hepatocytes[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(9): 22-28.
张亚蕾, 郑天慧, 刘伟, 等. 扶正化瘀方对原代大鼠肝细胞中CYP450的影响[J]. 中国实验方剂学杂志, 2018,24(9):22-28. DOI： 10.13422/j.cnki.syfjx.20180902.

ZHANG Ya-lei, ZHENG Tian-hui, LIU Wei, et al. Effect of Fuzheng Huayu Recipe on CYP450 in Primary Rat Hepatocytes[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(9): 22-28. DOI： 10.13422/j.cnki.syfjx.20180902.

摘要

目的：采用原代大鼠肝细胞（PRH）研究扶正化瘀方（FZHY）对大鼠细胞色素P450酶（CYP450）的影响。方法：采用两步灌流法分离大鼠原代肝细胞，形成肝板结构后加入FZHY共培养24 h，换成含有4种CYP450同工酶（CYP1A2，CYP2C9，CYP2D6，CYP3A4）对应的特异性探针药物（非那西丁、甲苯磺丁脲、氢溴酸右美沙芬、睾酮）的培养基，培养2 h后吸取上清液，利用UPLC-MS/MS对探针药物的代谢产物进行检测，考察FZHY对探针药物代谢产物生成量的影响，评价FZHY对PRH中CYP450代谢活力的影响。结果：PRH中CYP1A2，CYP2C9，CYP2D6与CYP3A4具有良好的代谢活力。4种探针药物在0~500 μmol·L-1内对PRH没有毒性，在0.5~500 μg·L-1时，FZHY对PRH没有毒性。FZHY在5 μg·L-1时对PRH具有轻微的保护作用，并能使甲苯磺丁脲的代谢活化值——米氏常数（Km）降低20.8%；氢溴酸右美沙芬的Km降低39.2%；非那西丁的Km降低17.4%；并使睾酮的Km显著降低。结论：FZHY能抑制原代大鼠肝细胞中CYP1A2，CYP2C9，CYP2D6和CYP3A4的代谢活性。

Abstract

Objective: Taking primary rat hepatocytes (PRH) model

to explore the effect of Fuzheng Huayu recipe (FZHY) on rat cytochrome P450 enzyme (CYP450). Method: PRH were isolated and cultured by two-step perfusion method.With the formation of the hepatic plate structure

FZHY was added to culture for 24 h

then replaced with culture medium containing specific probe substrates of CYP450 (phenacetin-CYP1A2

tolbutamide-CYP2C9

dextromethorphan hydrobromide-CYP2D6

testosterone-CYP3A4)

the supernatant was aspirated after 2 h

the corresponding products of the probe drugs were detected by UPLC-MS/MS. Result: CYP1A2

CYP2C9

CYP2D6 and CYP3A4 in PRH had good metabolic activity.The probe drugs had no toxicity on PRH in the range of 0-500 μmol · L-1

FZHY had no toxicity on PRH in the range of 0.5-500 μg · L-1.FZHY could slightly protect PRH with concentration of 5 μg · L-1.After PRH was cultured with 5 μg · L-1 FZHY for 24 h

Michaelis constant (Km) of tolbutamide decreased by 20.8%

Km of dextromethorphan hydrobromide decreased by 39.2%

Km of phenacetin decreased by 17.4%

Km of testosterone decreased significantly. Conclusion: FZHY can inhibit the activity of CYP1A2

CYP2C9

CYP2D6 and CYP3A4 in PRH.

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