四氢姜黄素改善多柔比星诱导的心脏毒性作用的研究

Experimental study on the effect of tetrahydrocurcumin on cardiotoxicity induced by doxorubicin

目的探究姜黄素衍生物四氢姜黄素(THC)能否减轻多柔比星(DOX)急性心脏毒性并初步阐明其作用机制。方法通过单次腹腔注射大剂量DOX建立急性心脏毒性小鼠模型,随后通过灌胃方式每日给予THC,剂量为100 mg/kg,共处理5天。实验小鼠分为对照(Control)组;THC组;DOX组;DOX+THC组。DOX处理5天后评估心肌病理改变、心脏收缩舒张功能、氧化应激损伤和凋亡情况。结果与Control组小鼠相比,DOX处理后,小鼠心肌细胞出现空泡变性,心脏收缩和舒张功能明显受损,活性氧(ROS)产量明显增高,心肌组织促凋亡蛋白Bax和cleaved-Caspase 3表达量、心肌凋亡率明显增加,而心肌组织抗凋亡蛋白Bcl-2表达量明显降低。四氢姜黄素处理可明显逆转DOX引起的上述心肌损伤(均P<0.05)。结论四氢姜黄素通过抑制氧化应激损伤和凋亡改善多柔比星急性心脏毒性。

Objective To investigate whether the curcumin derivative tetrahydrocurcumin(THC)could alleviate the acute cardiotoxicity of doxorubicin(DOX)and to elucidate its mechanism of action preliminarily.Methods The mouse model of acute cardiotoxicity was established by a single injection of DOX intraperitoneally,followed by daily administration of THC by gavage at a dose of100 mg/kg for 5 days.The experimental mice were divided into control group,THC group,DOX group and DOX+THC group.Myocardial pathological changes,cardiac systolic and diastolic function,oxidative stress injury and apoptosis were evaluated 5 days after DOX treatment.Results Compared with the control group,vacuolar degeneration of cardiomyocytes was observed while cardiac systolic and diastolic function was significantly impaired.The production of reactive oxygen species(ROS)and the expression levels of proapoptotic proteins Bax and cleaved-Caspase 3 in myocardial tissue were significantly increased,while the expression of anti-apoptotic protein Bcl-2 in myocardial tissue was significantly reduced after DOX treatment.Tetrahydrocurcumin treatment could markedly reverse the above-mentioned damages caused by DOX(all P<0.05).Conclusion Tetrahydrocurcumin can alleviate the acute cardiotoxicity of DOX by inhibiting oxidative stress damage and apoptosis.