盐酸阿霉素对大鼠心肌损伤的分子机制研究

Study of molecular mechanism of cardiac injury induced by adriamycin

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 1 0只) :正常对照组 ,ADR低剂量组 (1 0mg·kg-1) ,ADR中剂量组 (2 0mg·kg-1) ,ADR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 .0 5 ,P <0 .0 1 ) ;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、P1 0 5mRNA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。

AIM: To preliminarily study the molecular mechanism for the cardiac injury in rat by adriamycin and the mechanism for the acute repair in the body. METHODS: The male Sprague Dawley rats were randomly divided into four groups (n=10 in each): The first group was kept without treament and served as the control ;the second, the third and 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 quantitative reverse 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 enzyme activities 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, and it is supposed that FN and P105 are involved in the acute repair after the cardiac injury induced by ADR in the body through a serial of signal pathways.