硒对阿霉素致小鼠心脏毒性的保护作用.doc

硒对阿霉素致小鼠心脏毒性的保护作用 作者：徐卓立　郭军华　李盟军　梁月琴　魏树均 单位：徐卓立　魏树均（北京 100071 解 放军北京军医学院）；郭军华　李盟军　梁月琴（军事医学科学院附属医院临床药理室） 关键词：金属硫蛋白；阿霉素；硒；心脏毒性 摘要　目的：探讨含硒制剂诱导金属硫蛋白在对抗阿霉素心脏毒性中的 作用，比较 无机硒制剂亚硒酸钠与有机硒制剂硒。方法：不同时间给小鼠喂予硒制剂后取 血分离血清，按常规查GOT和CK活性，按DTNB法测GSH-Px活性；取心、肝、 肾组织按Hg-Chelex法测金属硫蛋白(MT)含量并做心脏病理学检查。结果：两种含硒 制剂均能减轻阿霉素引起的体重下降、GOT与CK酶升高及心脏病理损害 ，其中富 硒麦芽的效果略优于亚硒酸钠。两者还能增加GSH-Px酶活性，诱导心脏中MT合成 增加，连续使用硒制剂的整体效果优于先或后使用该制剂。结论：除升高GSH-Px外， 硒制剂诱导合成MT很可能是减轻阿霉素心脏毒性的保护机制之一。两种硒制剂比较 使用硒较亚硒酸钠更为安全，且不降低原已证实的亚硒酸钠对心肌的保护作 用 。 The protective action of Malt-Se to the cardiotoxicity of doxorubicin by Malt-Se Xu Zhuoli(Xu ZL)，Guo Junhua(Guo JH)，Li Mengjun(Li M J)，et al (Beijing Medical College of PLA,Beijing 100071)] ABSTRACT　OBJECTIVE：To study the effect of MT during N a2SeO3 and Malt-Se on the cardictoxicity produced by doxorubicin,and to compare organic and inorganic compounds containing-Se.METHODS:The meas urement of GOT and CK in blood serum and examination of the pathological heart d amage was done with routine methods.The GSH-Px activity in blood serum was assa yed by DTNB method.Hg-chelex method was used for determination of MT in heart,l iver and kidney.RESULTS:Both of the compounds can resist the toxicit ies of doxorubicin,such as the body weight decreased,GOT and CK increased and pa thological heart damage(P＜0.01 or P＜0.05＝.They also in crease the activity of GSH-Px(PP＜0.01＝ and induce metallothionein( MT) in heart,liver and kidney(P＜0.01 or P＜0.05＝.The ef fects of using the compounds continuously is better than that of preadministrati on or retroadministration.CONCLUSION:Those suggeste that GSH-Px and MT may all have the cardicprotective effects,and organic compound(Malt-Se) ma y be safer than inorganic one(Na2SeO3). KEY WORDS　metallothionein doxorubicin cardictoxicity selenium 金属硫蛋白(Metallothionein,MT)是一种能被诱导合成，并通过金属储存，自由基清除等环节对抗体内有害物质的特殊低分子非酶蛋白质。通过诱导MT这一特殊途径的 生理保护机制，达到防病治病或减低某些药物毒副作用的目的，已成为目前基础与临床研究的热点课题［1,2