摘要
目的:探究葛根素(Pue)能否减轻多柔比星(DOX)引起的心脏毒性及其具体机制。方法:通过一次性腹腔注射多柔比星(15 mg/kg)建立小鼠多柔比星心脏毒性急性模型。DOX给药前3 d每日通过腹腔注射给予SIRT_3特异性阻断剂3-TYP[50 mg/(kg·d)]给药3 d。DOX给药后每日通过腹腔注射给予葛根素[10 mg/(kg·d)],给药5 d。实验小鼠随机分为正常组(Control组),葛根素组(Pue组),多柔比星组(DOX组),多柔比星+葛根素组(DOX+Pue组),3-TYP+多柔比星+葛根素组(3-TYP+DOX+Pue组),3-TYP+多柔比星组(3-TYP+DOX组)。DOX给药5 d后检测小鼠心脏收缩舒张功能、心脏组织病理改变、血清LDH水平、氧化应激和凋亡情况。结果:与Control组小鼠相比,DOX组小鼠心功能明显受损,心肌细胞出现"空泡化"反应,血清内LDH水平、心肌组织心肌细胞内氧活性(ROS)产量、丙二醛(MDA)含量和心肌凋亡水平明显增加。葛根素给药可以有效减轻多柔比星心脏毒性,抑制心肌组织氧化应激损伤和凋亡,伴随SIRT_3/SOD_2信号的激活。而用SIRT_3特异性抑制剂3-TYP抑制SIRT_3信号通路后,葛根素的保护作用明显减弱(均P<0.05)。结论:葛根素可以通过激活SIRT_3/SOD_2信号通路抑制氧化应激损伤和凋亡缓解多柔比星心脏毒性。
Objective:To explore whether puerarin (Pue) can alleviate the cardiotoxicity caused by doxorubicin (DOX) and explore its specific mechanism. Methods:An acute model of doxorubicin-induced cardiotoxicity in mice was established by intraperitoneal injection of doxorubicin (15 mg/kg). SIRT 3-specific inhibitor 3-TYP (50 mg/kg/day) was administered intraperitoneally 3 days before DOX administration for 3 days. Pue [10 mg/(kg·day)] was administered intraperitoneally following DOX treatment for 5 days. The experimental mice were randomly divided into control group, Pue group, DOX group, DOX+Pue group, 3-TYP+DOX+Pue group and 3-TYP+DOX group. Mice were examined for cardiac systolic and diastolic function, cardiac histopathological changes, serum LDH level, oxidative stress and apoptosis 5 days after DOX administration. Results:compared with the control group, the mice in the DOX group showed a significant impaired cardiac function, and vacuolar degeneration in the cardiomyocytes. Besides, serum LDH level, ROS production, MDA content and myocardial apoptosis in the myocardium were significantly increased. Puerarin administration effectively ameliorated the cardiotoxicity of doxorubicin, inhibited the oxidative stress damage and apoptosis of myocardial tissue, accompanied by the activation of SIRT3/SOD2 signaling pathway. After inhibiting the SIRT 3 signaling pathway using the SIRT 3-specific inhibitor 3-TYP, the protective effects of puerarin were significantly attenuated (all P<0.05).Conclusion:Puerarin alleviated doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and apoptosis via activating the SIRT 3/SOD 2 signaling pathway.
作者
马超
郭万刚
马文帅
MA Chao;GUO Wangang;MA Wenshuai(Department of Cardiovascular Diseases, Tangdu Hospital, Air Force Medical University Xi’an 710038)
出处
《陕西医学杂志》
CAS
2019年第4期411-416,共6页
Shaanxi Medical Journal
基金
陕西省自然科学基础研究计划面上项目(2016JM8062)
