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. 2015:2015:952671.
doi: 10.1155/2015/952671. Epub 2015 Mar 9.

Shengmai injection improved doxorubicin-induced cardiomyopathy by alleviating myocardial endoplasmic reticulum stress and caspase-12 dependent apoptosis

Yu Chen  1 , Yong Tang  1 , Yin Xiang  1 , Yu-Quan Xie  1 , Xiao-Hong Huang  1 , Ya-Chen Zhang  1
Affiliations

Shengmai injection improved doxorubicin-induced cardiomyopathy by alleviating myocardial endoplasmic reticulum stress and caspase-12 dependent apoptosis

Yu Chen et al. Biomed Res Int. 2015.

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.

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Figures

Figure 1
Figure 1
Survival and serum BNP concentration across all groups: (a) survival and (b) serum BNP concentration. At the end of follow-up duration, there were 20 survivals in control group, 11 in DOX group, and 16 in DOX + SMI group, respectively. Compared to control group, * P < 0.05; compared to DOX group, # P < 0.05.
Figure 2
Figure 2
Echocardiography across all groups: (a) control group, (b) DOX group, (c) DOX + SMI group, (d) EF and FS, (e) LVIDs and LVIDd, (f) LVESV and LVEDV, (g) LVAWs and LVAWd, and (h) LVPWs and LVPWd. At the end of follow-up duration, there were 20 survivals in control group, 11 in DOX group, and 16 in DOX + SMI group, respectively. Compared to control group, * P < 0.05; compared to DOX group, # P < 0.05.
Figure 3
Figure 3
TUNEL assay across all groups (×400): (a) control group, (b) DOX group, (c) DOX + SMI group, and (d) quantitative analysis of myocardial apoptosis across all groups. The apoptotic nuclei were stained brown, while the normal ones were blue. At the end of follow-up duration, there were 20 survivals in control group, 11 in DOX group, and 16 in DOX + SMI group, respectively. Compared to control group, * P < 0.05; compared to DOX group, # P < 0.05.
Figure 4
Figure 4
The expressions of GRP78 and caspase-12 cross all the groups: (a) GRP78 mRNA expression, (b) caspase-12 mRNA expression, (c) GRP78 protein expression, and (d) caspase-12 protein expression. At the end of follow-up duration, there were 20 survivals in control group, 11 in DOX group, and 16 in DOX + SMI group, respectively. Compared to control group, * P < 0.05; compared to DOX group, # P < 0.05.
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References

    1. Octavia Y., Tocchetti C. G., Gabrielson K. L., Janssens S., Crijns H. J., Moens A. L. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. Journal of Molecular and Cellular Cardiology. 2012;52(6):1213–1225. doi: 10.1016/j.yjmcc.2012.03.006. - DOI - PubMed
    1. Chatterjee K., Zhang J., Honbo N., Karliner J. S. Doxorubicin cardiomyopathy. Cardiology. 2010;115(2):155–162. doi: 10.1159/000265166. - DOI - PMC - PubMed
    1. Takemura G., Fujiwara H. Doxorubicin-induced cardiomyopathy: from the cardiotoxic mechanisms to management. Progress in Cardiovascular Diseases. 2007;49(5):330–352. doi: 10.1016/j.pcad.2006.10.002. - DOI - PubMed
    1. Kumar D., Kirshenbaum L. A., Li T., Danelisen I., Singal P. K. Apoptosis in adriamycin cardiomyopathy and its modulation by probucol. Antioxidants & Redox Signaling. 2001;3(1):135–145. doi: 10.1089/152308601750100641. - DOI - PubMed
    1. Xu W. H., Son J., Wang Y., et al. Granulocyte colony-stimulating factor reduces cardiomyocyte apoptosis and improves cardiac function in adriamycin-induced cardiomyopathy in rats. Cardiovascular Drugs and Therapy. 2006;20(2):85–91. doi: 10.1007/s10557-006-7652-9. - DOI - PubMed

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