摘要
目的:研究硫酸锌诱导金属硫蛋白(MT)对阿霉素(DOX)致氧自由基产生的影响。方法:雄性野生型小鼠(MT+/+)及敲除MT基因的转基因小鼠(MT-/-)随机分成4组,即对照组、DOX组、锌预处理组、锌预处理+DOX组。动物单次腹腔注射DOX(15 mg.kg-1)或生理盐水(NS),此前24 h及48 h分别给予锌(ZnSO4,20 mg.kg-1,s.c.)或NS预处理。给药4 d后测定心脏组织超氧阴离子(O2.-)水平及还原型谷胱甘肽(GSH)含量,Westernblot检测内皮型一氧化氮合酶(eNOS)的表达情况。结果:DOX能显著增加MT+/+小鼠及MT-/-小鼠心脏组织中O2.-的生成,耗竭GSH,上调eNOS的表达水平,而且MT-/-小鼠变化更为明显。Zn预处理能显著降低DOX致MT+/+小鼠O2.-生成增加以及GSH耗竭,抑制DOX诱导的eNOS表达增强,但在MT-/-小鼠中无此效应。结论:MT可抑制DOX致氧自由基产生增加及GSH耗竭,此效应可能与eNOS表达改变有关。
AIM： To investigate the effect of metallo-thionein （MT） on Doxorubicin （DOX）-induced superoxide generation. METHODS： Male wild type （ MT ＋ / ＋ ） and metallothionein-null （MT-/-） mice were divided into 4 groups respectively and were pretreated with either saline orZnSO4（20 mg·kg^-1, s.c.） at 24 h and 48 h before a single administration of DOX （ 15 mg·kg^-1 , i. p. ） or equal volume of saline. Mice were sacrificed on the 4th day after treatment and their hearts were collected for analysis. RF^ULTS： Doxorubicin treatment significantly enhanced superoxide generation and depleted glutathione in MT ＋ / ＋ mice heart and these effects were even more severe in MT- / - mice. These toxic changes were greatly inhibited by zinc pretreatment in MT ＋/＋ mice heart but not in MT-/- mice. Furthermore, zinc pretreatment significantly inhibited DOX-induced promotion of eNOS in MT ＋ / ＋ mice while similar effect did not occurr in MT- / - mice. CONCLUSION： Metallothionein can inhibit DOX-induced enhancement of superoxide generation and protect the antioxidant defense system in mice heart, this effect is possibly associated with changes of eNOS expression.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2006年第7期725-728,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金资助项目(№30572281)
