甲基黄酮醇胺对阿霉素诱导的小鼠心肌损伤的保护作用及其机理

Protective effects of methylflavonolamine on myocardial injury induced by adriamycin in mice

目的 :研究甲基黄酮醇胺 (methylflavono lamine ,MFA)对阿霉素诱导的心肌损伤的保护作用及机理。方法 :用阿霉素 (adriamycin ,ADR )1.5mg·kg-1,隔日 1次ip ,共 10d ,诱导小鼠心肌损伤。所有受试动物给药前均描记肢体导联心电图 ,心电图异常的动物剔除。观察各组动物的心电图J点抬高、QRS时间和Q -T间期延长的程度、血清磷酸肌酸激酶 (CK)、血清乳酸脱氢酶 (LDH)和心肌脂质过氧化产物丙二醛 (MDA)的含量及超氧化物歧化酶 (SOD)活性的变化。血清磷酸肌酸激酶、血清乳酸脱氢酶用比色法测定 ,超氧化物歧化酶用羟胺法测定 ,丙二醛用硫代巴比妥酸 (TBA)法测定。结果 :阿霉素可使小鼠的心电图J点异常抬高 ,QRS时间和Q T间期延长 ,小鼠血清CK、LDH含量增加 ,表明阿霉素可引起小鼠心肌细胞广泛损伤 ,阿霉素诱导小鼠心肌损伤模型成立。甲基黄酮醇胺能逆转ADR效应 ,能减轻小鼠急性心肌损伤时ECG的异常变化 ,降低血清LDH与CK含量 ,使心肌损害减轻。同时 ,阿霉素可以降低心肌组织中SOD的活性 ,增加心肌组织中MDA的含量 ,而甲基黄酮醇胺能增加心肌组织SOD活性 ,降低心肌组织中MDA含量 ,表明ADR的心脏毒性是由于诱导心脏产生自由基所致 ,而甲基黄酮醇胺则通过清除氧自由基和抗脂质过氧化作用来保护心肌细胞免受损伤?

AIM: To investigate the protective effects and mechanisms of methylflavonolamine (MFA) on myocardial injury induced by adriamycin in mice. METHODS: The myocardial injury was induced by adriamycin (ADR) 1.5 mg·kg -1 ip once every two days for ten days in mice. All mice were taken the electrocardiogram examination before given drugs. The mice with abnormal electrocardiogram were excluded prior to the experiment. The degree of J point elevation, the prolonged degree of the QRS complex duration and the Q T interval, the change of contents of serum creatine phosphokinase (CK), serum lactate dehydrogenase (LDH), myocardial malondialdehyde (MDA), and the activity of myocardial superoxide dismutase (SOD) were observed in control and treated groups. The contents of serum CK and LDH were measured by spectrophotometry, and the content of myocardial MDA was measured by TBA method and the activity of myocardial SOD by hydroxylamine method. RESULTS: The J point was elevated, the Q T interval and the duration of QRS complex were prolonged and the contents of serum CK and LDH were increased in mice with acute myocardial injury induced by ADR, suggesting that a widespread and severe myocardial cell injury occurred in the prepared models. While all these injury indices were reversed by MFA treatment. The content of myocardial MDA was increased and the activity of myocardial SOD was decreased in mice with myocardial injury, and MFA decreased the MDA content and increased the SOD activity, indicating that it possesses the actions of scavenging free oxygen radicals and anti lipoperoxidation. CONCLUSIONS: MFA significantly alleviates the degree of the acute myocardial injury in mice induced by ADR. Its mechanism may be associated with reducing oxygen free radical production and anti lipoperoxidation.