Tetrandrine Attenuated Doxorubicin-Induced Acute Cardiac Injury in Mice
Tetrandrine Attenuated Doxorubicin-Induced Acute Cardiac Injury in Mice
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粉防己碱可减轻阿霉素引起的小鼠急性心脏损伤
DOI：
10.1155/2020/2616024
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发表时间：
2020-05-09
影响因子：
--
通讯作者：
Wu, Lin
中科院分区：
文献类型：
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作者：
Li, Gang;Li, Wen-Rui;Wu, Lin
氧化损伤与阿霉素(DOX)心脏毒性的发生密切相关。已有报道，粉防己碱通过抑制ROS依赖的信号通路来预防小鼠心肌肥厚的发生。然而，粉防己碱是否能减轻DOX相关的心脏毒性尚不清楚。为探讨汉防己甲素的保护作用，小鼠在注射多西他汀前一天开始连续4d灌胃给予汉防己甲素(50 mg/kg)。小鼠一次性腹腔注射多柔比星(15 mg/kg)造成急性心脏损伤。我们研究中的数据显示，粉防己碱防止了DOX相关的全身消瘦和心脏萎缩，减少了心脏损伤的标志物，并改善了小鼠的心功能。此外，补充粉防己碱可保护小鼠免受氧化损伤和心肌细胞凋亡。在体外DOX暴露后，补充粉防己碱也减少了ROS的产生，提高了细胞的存活率。我们还发现，在体内和体外，粉防己碱补充增加了核因子(红系衍生2)样2(Nrf2)的表达和活性。补充粉防己碱可阻断Nrf2缺乏对小鼠的保护作用。总之，我们的研究发现粉防己碱可以改善心功能，并通过激活Nrf2来预防DOX相关性心脏损伤的发展。
Oxidative damage is closely involved in the development of doxorubicin- (DOX-) induced cardiotoxicity. It has been reported that tetrandrine can prevent the development of cardiac hypertrophy by suppressing reactive oxygen species- (ROS-) dependent signaling pathways in mice. However, whether tetrandrine could attenuate DOX-related cardiotoxicity remains unclear. To explore the protective effect of tetrandrine, mice were orally given a dose of tetrandrine (50 mg/kg) for 4 days beginning one day before DOX injection. To induce acute cardiac injury, the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg). The data in our study showed that tetrandrine prevented DOX-related whole-body wasting and heart atrophy, decreased markers of cardiac injury, and improved cardiac function in mice. Moreover, tetrandrine supplementation protected the mice against oxidative damage and myocardial apoptotic death. Tetrandrine supplementation also reduced ROS production and improved cell viability after DOX exposure in vitro. We also found that tetrandrine supplementation increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and activity in vivo and in vitro. The protection of tetrandrine supplementation was blocked by Nrf2 deficiency in mice. In conclusion, our study found that tetrandrine could improve cardiac function and prevent the development of DOX-related cardiac injury through activation of Nrf2.