Abstract
Background. Apoptosis plays vital roles in the progression of doxorubicin-induced cardiomyopathy (DOX-CM). Endoplasmic reticulum stress (ER stress) could induce specific apoptosis by caspase-12 dependent pathway. Shengmai Injection (SMI), a famous Traditional Chinese Medicine, could alleviate the heart damage via inhibiting myocardial apoptosis. However, it is unknown whether SMI can alleviate ER stress and its specific apoptosis in the setting of DOX-CM. Objective. To explore the effects of SMI on heart function, myocardial ER stress, and apoptosis of DOX-CM rats. Methods. Rats with DOX-CM were treated by SMI. Heart function was assessed by echocardiography and brain natriuretic peptide. Myocardial apoptosis was detected by TUNEL assay. ER stress was assessed by detecting the expressions of GRP78 and caspase-12. Results. At the end of eight-week, compared to control, significant heart dysfunction happened in DOX group. The ratio of apoptotic cardiomyocytes and the expressions of GRP78 and caspase-12 increased significantly (P < 0.05). Compared to DOX group, the apoptotic ratio and the expressions of GRP78 and caspase-12 significantly decreased in DOX + SMI group (P < 0.05), accompanied with improved heart function. Conclusion. SMI could alleviate myocardial ER stress and caspase-12 dependent apoptosis, which subsequently helped to improve the heart function of rats with DOX-CM.
Highlights
Doxorubicin (DOX) is a commonly used chemotherapeutic in clinic
Its application was greatly limited by the cardiotoxicity, which could lead to doxorubicin-induced cardiomyopathy (DOX-CM), one of the severest complications of DOX [1, 2]
We explored the effects of Shengmai Injection (SMI) on heart function, myocardial ER stress, and apoptosis of DOX-CM rats
Summary
Doxorubicin (DOX) is a commonly used chemotherapeutic in clinic. its application was greatly limited by the cardiotoxicity, which could lead to doxorubicin-induced cardiomyopathy (DOX-CM), one of the severest complications of DOX [1, 2]. Apoptosis plays vital roles in the progression of doxorubicin-induced cardiomyopathy (DOX-CM). Shengmai Injection (SMI), a famous Traditional Chinese Medicine, could alleviate the heart damage via inhibiting myocardial apoptosis. It is unknown whether SMI can alleviate ER stress and its specific apoptosis in the setting of DOX-CM. To explore the effects of SMI on heart function, myocardial ER stress, and apoptosis of DOX-CM rats. Compared to DOX group, the apoptotic ratio and the expressions of GRP78 and caspase-12 significantly decreased in DOX + SMI group (P < 0.05), accompanied with improved heart function. SMI could alleviate myocardial ER stress and caspase-12 dependent apoptosis, which subsequently helped to improve the heart function of rats with DOX-CM
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