盐酸阿霉素对大鼠心肌损伤的分子机制研究

A Study of Molecular Mechanism of Myocardial Damage by Adriamycin

目的 研究盐酸阿霉素对大鼠心肌损伤的分子机制。方法 将雄性SD大鼠 40只随机分成 4组 (每组 10只 ) :对照组 ,盐酸阿霉素低剂量组 (10mg·kg-1) ,盐酸阿霉素中剂量组 (2 0mg·kg-1) ,盐酸阿霉素高剂量组(4 0mg·kg-1) ,对后 3组分别一次性腹腔注射不同剂量的盐酸阿霉素 ,制备大鼠心肌损伤模型。采用硫代巴比妥酸(TBA)荧光分光光度法测定大鼠血清脂质过氧化产物丙二醛含量。并分别测定铜—锌超氧化物歧化酶和谷胱甘肽过氧化物酶的酶活性 ;运用RT PCR方法分析相关基因的表达。结果 盐酸阿霉素中、高剂量组大鼠血清中丙二醛含量高于对照组 (P <0 .0 5 ,P <0 .0 1) ;实验组铜—锌超氧化物歧化酶和谷胱甘肽过氧化物酶的酶活性均较对照组降低 ,其基因表达随盐酸阿霉素剂量的增加而不同程度的下调。

Objective To explore the molecular mechanism of myocardial damage in rat induced by adriamycin .Methods The male Sprague-Dawley rats were randomly divided into four groups(n=10 in each):The first group was served as control ;the other three groups received ADR with different doses (10 mg·kg -1,20 mg·kg -1,40 mg·kg -1, respectively) by intraperitoneal injections . The content of malondialdehyde(MDA)in the serum was measured by the method of thiobarbituric acid fluorometer. The expressions of copper, zinc-superoxide dismutase (Cu-Zn-SOD) genes and glutathione peroxidase(GSH-Px)gene were analyzed by using semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR).Results MDA contents in the sera of rats in moderate and high ADR groups were higher than that in the control group (P<0.05,P<0.01). The enzyme activities of Cu-Zn-SOD and GSH-Px in the moderate and high ADR dose groups were lower than that in the control group respectively(P<0.01), and the expression of their genes was also decreased with the increase of ADR doses.Conclusion The changes of the expression of Cu-Zn-SOD and GSH-Px genes may be one of the molecular mechanism for the myocardial damage induced by adriamycin .