天津医药

天津医药 ›› 2017, Vol. 45 ›› Issue (9): 912-916.doi: 10.11958/20170616

• 实验研究 • 上一篇    下一篇

异甘草酸镁对雷公藤甲素损伤 L-02 细胞中 UGT1A、MRP2 蛋白及其 mRNA 表达的影响

张靖，朱胜楠，谭亲友   

  1. 桂林医学院（邮编 541001）
  • 收稿日期:2017-06-01 修回日期:2017-07-03 出版日期:2017-09-15 发布日期:2017-09-25
  • 通讯作者: 谭亲友 E-mail:jsbzdqsmmz@126.com
  • 基金资助:
    基于PXP/CAR信号通路调控UGTs和MRP3探讨甘草配伍减毒机制;基于Nrf2/ARE 信号通路调控UGTs 和MRP3 探讨甘草的 配伍减毒机制;基于PXR/CAR信号通路调控UGT和P-gp探讨甘草的配伍解毒基制;基于PXR/CAR信号通路调控UGTs和MRP2探讨甘草的配伍减毒机制;基于Nrf2/ARE 信号通路调控UGTs 和MRP2 探讨甘草的 配伍减毒机制

Effects of magnesium isoglycyrrhizinate on the expressions of UGT1A, MRP2 protein and mRNA in L-02 cells damaged by triptolide

ZHANG Jing, ZHU Sheng-nan, TAN Qin-you   

  • Received:2017-06-01 Revised:2017-07-03 Published:2017-09-15 Online:2017-09-25

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摘要： 摘要：目的 研究异甘草酸镁对雷公藤甲素损伤 L-02 细胞中尿苷二磷酸葡萄糖醛酸转移酶 1A（UGT1A）和多 药耐药相关蛋白 2（MRP2）蛋白及其 mRNA 表达的影响，从药物代谢学方面探讨异甘草酸镁的保肝作用机制。方 法 L-02 细胞分为空白对照组、雷公藤甲素组、异甘草酸镁组、利福平组，共 4 组（n=6），空白对照组和雷公藤甲素组 仅加入培养基，异甘草酸每组和利福平组分别给予异甘草酸镁、利福平预处理 24 h，后 3 组再加入雷公藤甲素 18 h 后，用 MTT 法测定细胞存活率，用 Western blot 及 RT-PCR 检测各组细胞中 UGT1A、MRP2 蛋白及其 mRNA 表达水 平。结果 异甘草酸镁预保护 24 h 实验组的细胞存活率明显高于雷公藤甲素组（P＜0.05）；雷公藤甲素组 UGT1A、 MRP2 蛋白及其 mRNA 表达水平显著低于空白对照组（P＜0.05）；异甘草酸镁组 UGT1A、MRP2 蛋白及 mRNA 表达 水平较雷公藤甲素组显著升高（P＜0.05）；利福平组 UGT1A 蛋白及 mRNA 表达水平明显低于异甘草酸镁组（P＜ 0.05），MRP2 蛋白及 mRNA 表达水平与异甘草酸镁组差异无统计学意义。结论 异甘草酸镁可减轻雷公藤甲素对 L-02 细胞的损伤作用，其机制可能与诱导 UGT1A、MRP2 的表达有关。

关键词: 雷公藤属, 多药耐药相关蛋白质类, 异甘草酸镁, 雷公藤甲素, 尿苷二磷酸葡萄糖醛酸转移酶 1A, MRP2, L-02 细胞

Abstract: Abstract: Objective To observe the effect of magnesium isoglycyrrhizinate on the expressions of UGT1A, MRP2 protein and mRNA of L- 02 cells damaged by triptolide, and to investigate hepatoprotective mechanism of magnesium isoglycyrrhizinate in terms of drug metabolism. Methods L-02 cells were divided into 4 groups: normal group, triptolide group, magnesium isoglycyrrhizinate group and rifampicin group. Magnesium isoglycyrrhizinate group and rifampicin group were pretreated by magnesium isoglycyrrhizinate and rifampicin for 24 h and the remaining two groups added medium. Triptolide were added for 18 h except normal group. Cell survival rate was tested by MTT. The expression levels of UGT1A, MRP2 protein and mRNA were detected by Western blot assay and RT-PCR. Results Compared with triptolide group, cell survival rate was significantly higher in magnesium isoglycyrrhizinate group (P＜0.05). Meanwhile, the expression levels of UGT1A, MRP2 protein and mRNA were significantly lower in triptolide group compared with those of control group (P＜ 0.05). The expression levels of UGT1A, MRP2 protein and mRNA were significantly up- regulated in magnesium isoglycyrrhizinate pretreatment group than those of triptolide group (P＜0.05). The UGT1A protein and mRNA expressions were significantly decreased in rifampicin pretreatment group than those of magnesium isoglycyrrhizinate group (P＜0.05), but there were no significant differences in MRP2 protein and mRNA expressions between the two groups. Conclusion Magnesium isoglycyrrhizinate shows protective effects on triptolide induced L-02 cell injury, which may be involved with the activation of UGT1A and MRP2.

Key words: tripterygium, multidrug resistance- associated proteins, magnesium isoglycyrrhizinate, triptolide, uridine, diphosphate glucuronyltransferase 1A, MRP2, L-02 cell