阿霉素致大鼠心肌线粒体DNA突变及硒的保护作用

Mitochondrial DNA injuries induced by adriamycin and selenium protective action in rat cardiomyocytes

采用ＰＣＲ方法对大鼠心肌ｍｔＤＮＡ特异片段进行扩增，用ＰＣＲ－ＳＳＣＰ和薄层扫描方法检测其片段的缺失突变和点突变。阿霉素组大鼠心肌ｍｔＤＮＡ特异片段出现缺失突变（６０．５％），并有点突变（２／６）。Ｓｅ保护组检出部分缺失突变（３０．０％），未检出点突变。阿霉素可以导致大鼠心肌ｍｔＤＮＡ突变热点区域发生缺失突变和点突变。ｍｔＤＮＡ损伤可能是阿霉素致心肌损伤的重要机制之一。Ｓｅ可以降低阿霉素对ｍｔＤＮＡ的损伤，对阿霉素性心肌损伤有明显地保护作用。

The damaged effects of adriamycin to cardiomyocytes mainly acted on the myocardial mitochondria,but the mutation occurred at a much higher rate in the mitochondrial DNA(mtDNA).The damage of mt DNA would deteriorate oxidative phosphorylation (OXPHOS) and energy metabolism.By using PCR,PCRSSCP and Thinlayer plate densitometry,we examined the specially designated fragments of the mtDNA.The mt DNA fragments of rat cardiomyocytes in adriamycin group showed deletion mutation(60.5%) and point mutations(2/6).Se group had part deletion mutation (30.3%) and no point mutation.Adriamycin could induce cardiomyocyte mt DNA mutations,including deletion mutation and point mutation.We considered that mt DNA injuries might be the one of important mechanisms of Adriamycin damage to the cardiomyocytes.Se had a clearly protective action to myocardial injuries induced by adriamycin.