L-甲状腺素增强氧化应激及四氢小檗碱衍生物CPU86017的对抗作用  

The Oxidative Stress Enhancing Effects by L-thyroxin and the Antioxidant Effects of CPU 86017, A Derivative of Tetrahydroberberine

作　　者：郝静梅[1] 戴德哉[1] 于锋[1] 

机构地区：[1]中国药科大学药理学研究室,江苏南京210009

出　　处：《药学进展》2005年第9期417-421,共5页Progress in Pharmaceutical Sciences

基　　金：国家自然科学基金资助项目(30230170)

摘　　要：目的:探讨L-甲状腺素对氧化应激状态的诱导作用及四氢小檗碱衍生物CPU86017的抗氧化应激作用.方法:将实验大鼠分为正常组、L-甲状腺素组(L-甲状腺素0.4 mg/kg,ip,连续10天)和CPU86017治疗组(L-甲状腺素0.4 mg/kg,ip,连续10天.第8～10天时,加用 CPU86017 80 mg/kg,po),至第11天时,取其肾脏制匀浆和线粒体液,测定匀浆中谷胱甘肽过氧化物酶(GSH-PX)、黄嘌呤氧化酶(XOD)和过氧化氢酶(CAT)的活性,判别L-甲状腺素是否能造成模型动物的氧化应激状态.在各组肾线粒体液中分别加入Fenton 's试剂,测定肾线粒体液中的MDA含量,判断Fenton 's试剂对不同组肾线粒体的氧化应激损伤程度.结果:甲亢大鼠肾脏组织中氧化应激呈明显增强状态,其MDA和XOD活性增强;GSH-PX和CAT活性降低.CPU86017可明显改善氧化应激,并且在体外能部分对抗Fenton 's试剂对大鼠肾线粒体的脂质过氧化反应.结论:L-甲状腺素能明显增强氧化应激;而CPU86017具有良好的体内、外抗氧化应激作用.Objective： To investigate the oxidative stress enhancing effects by L-thyroxin and the antioxidant effects of CPU 86017, a derivative of tetrahydroberberine. Methods： 24 rats were divided into control group, L-thyroxin group （0.4 mg/kg of L-thyroxin, × 10 d,ip） and CPU 86017 group（0.4 mg/kg of L-thyroxin, ×10 d, ip and added CPU 86017 from 8th to 10th day, po）. At 11th day, the rats＇ renel homogenates were prepared and the activities of XOD （xanthine oxidase）, GSH-PX （glutathione peroxidase ） and CAT （catalase） were conducted to evaluate the oxidative stress in rats. The Fenton＇s reaction induced oxidative stress in vitro was also applied. Fenton＇s agent was added into the renal mitochondrial preparations of three groups separately, and the activities of MDA （malondialdehyde） of the renal mitochondrial preparations in three groups were measured. Results： Oxidative stress in the renal tissue was significantly enhanced by L- thyroxin. The activities of MDA and XOD increase in production, and the activities of GSH-PX and CAT decrease. A remarkable improvement of oxidative stress was achieved by CPU 86017, and the lipid peroxidation in the renal mitochondrial was suppressed partially by CPU 86017 in vitro. Conclusion： L- thyroxin enhances oxidative stress significantly and CPU 86017 possesses substantial effect to suppress oxidative stress in vivo and in vitro.

关 键 词：氧化应激 L-甲状腺素 CPU86017 

分 类 号：R96[医药卫生—药理学]