Preliminary study on the alleviating effects of muscone on doxorubicin⁃induced cardiotoxicity
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摘要:
目的：评估麝香酮（muscone）对多柔比星（doxorubicin，DOX）诱导的心毒性作用的影响，并探讨其可能机制。方法：成年雄性C57BL/6小鼠24只，随机分为4组：生理盐水组（control组，4只）、生理盐水+麝香酮组（muscone组，4只）、多柔比星+生理盐水组（DOX组，8只）和多柔比星+麝香酮组（DOX+muscone组，8只），药物处理后饲养5周，于药物处理前、药物处理后第2周、第5周心超检测左室射血分数（left ventricular ejection fraction，LVEF），第6周处死小鼠分离心脏组织，通过免疫组织化学染色、实时定量聚合酶链反应（quantitative real time polymerase chain reaction，qRT-PCR）检测Bax、Bcl-2、cleaved-caspase-3的表达水平。H9C2细胞分4组（control组、muscone组、DOX组、DOX+muscone组），药物处理24 h，Western blot检测Bax、Bcl-2、caspase-3、cleaved-caspase-3的表达水平。结果：与control组相比，muscone组心功能、凋亡指标无明显变化，DOX组小鼠心功能下降，在小鼠心肌细胞及H9C2细胞中，Bax、cleaved-caspase-3表达明显上升（P＜0.05）、Bcl-2表达明显下降（P＜0.05）。与DOX组相比，DOX+muscone组小鼠心功能降低不明显，在小鼠心肌细胞及H9C2细胞中Bax、cleaved-caspase-3表达上升趋势反转（P＜0.05）、Bcl-2表达增多（P＜0.05）。结论：麝香酮在多柔比星诱导的心肌损害中起保护作用，可以减轻多柔比星诱导的心肌细胞凋亡。
Abstract:
Objective：This study aims to evaluate the effect of muscone on the cardiotoxicity induced by doxorubicin（DOX） and explore its possible mechanism. Methods：Total 24 adult male C57BL/6 mice were randomly divided into 4 groups：normal saline group（control group，n=4），normal saline + muscone group（muscone group，n=4），doxorubicin + normal saline group（DOX group，n=8）and doxorubicin + muscone group（DOX + muscone group，n=8），reared for 5 weeks after drug treatment. Left ventricular ejection fraction（LVEF）was detected by cardiac ultrasonography before drug treatment，2 weeks after drug treatment and 5 weeks after drug treatment. Mouse was executed 6 weeks after drug treatment，and the isolated heart tissue was collected to detect the expression levels of Bax，Bcl-2，and cleaved-caspase-3 by immunohistochemical staining and quantitative real time polymerase chain reaction. H9C2 cells were divided into 4 groups（control group，muscone group，DOX group，DOX + muscone group） according to drug treatment for 24 hours，and the expression levels of Bax，Bcl-2，caspase-3，and cleaved-caspase-3 were assessed by Western blot. Results：Compared with the control group. The muscone group had no significant changes in cardiac function and apoptotic indicators. The cardiac function of the mice in the DOX group decreased. The expressions of Bax，cleaved-caspase-3 increased significantly（P < 0.05），and the expression of Bcl-2 decreased significantly（P＜0.05）in mouse cardiomyocytes and H9C2 cells. Compared with the DOX group，the heart function of the mice in the DOX + muscone group was not significantly reduced，the upward trend of Bax and cleaved-caspase-3 expression was reversed（P＜0.05），and Bcl-2 expression was increased（P＜0.05）in mouse cardiomyocytes and H9C2 cells. Conclusion：Muscone plays a protective role in myocardial damage induced by doxorubicin，and can reduce myocardial cell apoptosis induced by doxorubicin.
