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目的探讨褪黑素(Mel)对多柔比星(DOX)心脏毒性的治疗作用及其对内质网应激的影响。方法 60只雄性C57BL/6小鼠20~25 g,随机分为3组(每组n=20):正常对照(Control)组、DOX组和DOX与Mel共处理(DOX+Mel)组。给予小鼠单次腹腔注射DOX,剂量为15 mg/kg。DOX处理后5天,检测心功能、心率、心脏凋亡比例以及内质网应激水平。结果DOX显著下调左室射血分数(LVEF)与左室短轴缩短率(LVFS),引起心肌损伤,下调心率,增加心肌细胞凋亡比例。Mel可显著改善DOX引起的心脏收缩功能障碍,减轻心肌损伤,上调心率,并降低心肌细胞凋亡比例。此外,Mel治疗可显著抑制DOX诱发的心肌内质网应激,从而缓解心肌损伤(P均<0.05)。结论 Mel共处理可显著抑制DOX诱发的内质网应激过度激活,减轻心肌细胞凋亡,从而抵抗DOX心脏毒性。
Objective To investigate the therapeutic effect of melatonin on cardiotoxicity of doxorubicin (DOX) and its effect on endoplasmic reticulum stress. Methods Sixty male C57BL / 6 mice (20-25 g) were randomly divided into 3 groups (n = 20 in each group): control group, DOX group and DOX + Mel group. Mice were given a single intraperitoneal injection of DOX at a dose of 15 mg / kg. Five days after DOX treatment, cardiac function, heart rate, cardiac apoptotic ratio, and endoplasmic reticulum stress levels were examined. Results DOX significantly down-regulated left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), caused myocardial damage, decreased heart rate and increased cardiomyocyte apoptosis ratio. Mel significantly improved DOX-induced cardiac contractile dysfunction, decreased myocardial injury, increased heart rate, and decreased cardiomyocyte apoptosis. In addition, Mel treatment can significantly inhibit DOX-induced myocardial endoplasmic reticulum stress, thereby relieving myocardial injury (all P <0.05). Conclusion Mel co-treatment can significantly inhibit DOX-induced endoplasmic reticulum stress over-activation, reduce myocardial apoptosis and thus resist DOX cardiotoxicity.