延胡索酸二甲酯对大鼠醌还原酶和谷胱甘肽-S-转移酶的诱导作用

Induction of Quinone Reductase and Glutathion s transferase by Dimethyl Fumarate in Rats

目的 探讨延胡索酸二甲酯（ＤＭＦ） 对大鼠主要脏器醌还原酶和谷胱甘肽Ｓ转移酶的诱导作用和意义。方法 雄性Ｗｉｓｔａｒ 大鼠饮食中补充０ ．２ ％ ＤＭＦ，于６ 、２４ 、７２ 小时、１ 和２ 周后取血并处死动物，用酶动力学法测定大鼠腺胃、肝、肺、肾和心脏中的醌还原酶（ＱＲ） 和谷胱甘肽Ｓ转移酶（ＧＳＴｓ） 活性，并按此法测定血清ＱＲ、ＧＰＴ和乳酸脱氢酶含量。结果 服用ＤＭＦ２４ 、７２ 小时、１ 和２ 周后可观察到腺胃、肝、肺、肾脏中ＱＲ 和ＧＳＴｓ 活性显著增高（ Ｐ＜ ０ ．０００ １ 或Ｐ＜ ０ ．０１） ，同时血清ＱＲ 活性也显著增高（ Ｐ＜ ０ ．０１ ，或Ｐ＜ ０ ．０００ １） 。ＤＭＦ对血清ＧＰＴ 和乳酸脱氢酶的活性则无影响。结论 ＤＭＦ对大鼠腺胃、肝、肺、肾和血清中的ＱＲ 和ＧＳＴｓ 活性具有诱导作用，ＤＭＦ有望成为人类抗氧化损伤的保护剂和解毒剂。

Objective To assess induction of quinone reductase (QR) and glutathion s transferases (GSTs) by dimethyl fumarate (DMF) in major viscera of rats. Methods Fodder fed to male Wistar rats was supplemented with 2.0% DMF, and blood specimens were collected form the rats 6 h, 24 h, 72 h, 1 week and 2 weeks after feeding, respectively, and then animals were killed. QR and GSTs activities were determined in rats' gland stomach, liver, lung, kidney and heart, and also QR, LDH and GPT activities in their sera were measured with enzyme dynamic methods. Results Administration of DMF for 24 h, 72 h, 1 week and 2 weeks in rats can significantly increase activities of QR and GSTs in their gland stomach, liver, lung and kidney, as compared with those in controls ( P <0.000 1, or P <0.01), and their serum QR also significantly increased ( P <0.000 1, or P <0.01). But, DMF had no effect on activities of serum GPT and LDH ( P >0.05). Conclusion DMF is a potent induction agent for QR and GSTs in the gland stomach, liver, lung and kidney of rats, which suggests it will hopefully be a protective and antidotic agent against human antioxidant injury.