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中国临床药理学与治疗学 ›› 2002, Vol. 7 ›› Issue (3): 209-212.

• 基础研究 • 上一篇    下一篇

盐酸阿霉素对大鼠心肌损伤的分子机制研究

李咏梅, 宋伯根, 赵桂芬, 沈丽贤   

  1. 同济大学医学院病理教研室, 上海 200331
  • 收稿日期:2001-12-31 修回日期:2002-04-02 发布日期:2020-12-01

Study of molecular mechanism of cardiac injury induced by adriamycin

LI Yong-Mei, SONG Bo-Gen, ZHAO Gui-Fen, SHEN Li-Xian   

  1. Department of Pathology, Medical School Tongji University, Shanghai 200331
  • Received:2001-12-31 Revised:2002-04-02 Published:2020-12-01

摘要: 目的: 初步研究盐酸阿霉素(adriamycin,ADR)对大鼠心肌损伤的分子机制及机体急性修复的机理。方法: 将雄性SD 大鼠40 只随机分成4 组(每组10只):正常对照组,ADR 低剂量组(10 mg·kg-1), ADR中剂量组(20mg·kg-1),ADR 高剂量组(40 mg·kg-1),对后3 组分别一次性腹腔注射不同剂量的ADR, 制备大鼠心肌损伤模型。采用硫代巴比妥酸(TBA) 荧光分光光度法测大鼠血清丙二醛(malondialdehyde,MDA) 含量;采用黄嘌呤氧化酶法测定铜锌超氧化物歧化酶(Cu-Zn-SOD) 活性;采用二硫代二硝基苯甲酸直接显色法测定谷胱苷肽过氧化物酶GSH-Px 活性;运用RT-PCR 方法分析相关基因的表达。结果: ADR中、高剂量组大鼠血清中MDA 含量高于对照组(P<0.05, P<0.01);实验组Cu-Zn-SOD 和GSH-Px 的酶活性均较对照组降低, 并与其基因表达的减弱呈密切的相关性;FN 、P105 mRNA 在不同剂量模型组呈不同程度的高表达。结论: 抗氧化酶基因表达的改变可能是ADR 导致心肌损伤的分子机制之一, 而纤连蛋白和核转录因子可能通过一系列的信号转导参与了机体损伤后急性期的修复。

关键词: 盐酸阿霉素, Cu-Zn-SOD, GSH-Px, 纤连蛋白, P105, 基因表达, 心脏, 大鼠

Abstract: AIM: To preliminarily study the molecular mechanism for the cardiac injury in rat by adriamycin and the mechanism for the acuterepair in the body.METHODS: The male Sprague-Dawley rats were randomly dividedintofour groups (n =10 in each):The first group was kept without treament and served as the control;the second, the thirdand the fourth received ADR in different doses (10, 20, 40 mg·kg-1, respectively) by injection of adriamycin.The content of malondialdehyde (MDA) in the serum was estimated with thiobarbituric acid.Cu-Zn-SOD was measured by its reaction with xanthine oxidase.GSH was measured by its reaction with 5, 5-nitrobenzoic acid. Using semi-quantitativereverse transcription-polymerase chain reaction (RT-PCR), we analyzed the expression of the associated gene.RESULTS: MDA contents in the medium and high ADR dose groups were higher than that in the control group (P<0.05, P<0.01).FN mRNA and P105 mRNA had different extents higher expression in different doses groups compared to normal rats.The enzymeactivities of copper, zinc-superoxide dismutase (Cu-Zn-SOD) and glutathione peroxidase(GSH-Px) in the medium and high ADR dose groups were lower than that in control group respectively (P<0.01), and were positively correlated with the expression of their gene.CONCLUSION: The changes of the expression of Cu-Zn-SOD and GSH-Px may be one of the molecular mechanism for the cardiotoxicity by adriamycin, andit is supposed that FNand P105 are involvedin the acuterepair after the cardiac injury induced by ADR in the body through a serial of signal pathways.

Key words: adriamycin, Cu-Zn-SOD, GSH-Px, fibronectin, P105, gene expression, heart, rats

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