Key result
Shenmai Injection improved cardiac structure and function and inhibited excessive autophagy in a rat model of doxorubicin cardiotoxicity by increasing miR-30a and decreasing Beclin 1 mRNA (P<0.01).
Why the study?
The potential protective mechanism of Shenmai Injection on cardiotoxicity caused by anthracyclines was not clear.
Does Shenmai injection improve doxorubicin-induced cardiotoxicity in a rat model?
Does Shenmai injection improve doxorubicin-induced cardiotoxicity in a rat model?
p-value: p=< 0.01
Shenmai injection alleviates doxorubicin-induced cardiotoxicity in rats by inhibiting excessive autophagy through the regulation of the miR-30a/Beclin 1 pathway.
Hypothesis-generating in rat doxorubicin cardiotoxicity models; leaves open translation of SMI to clinical use.
BACKGROUND: Shenmai Injection (SMI) has been widely used in the treatment of cardiovascular diseases and can reduce side effects when combined with chemotherapy drugs. However, the potential protective mechanism of SMI on the cardiotoxicity caused by anthracyclines has not been clear. METHODS: We used network pharmacology methods to collect the compound components in SMI and myocardial injury targets, constructed a 'drug-disease' target interaction network relationship diagram, and screened the core targets to predict the potential mechanism of SMI in treating cardiotoxicity of anthracyclines. In addition, the rat model of doxorubicin cardiotoxicity was induced by injecting doxorubicin through the tail vein. The rats were randomized in the model group, miR-30a agomir group, SMI low-dose group, SMI high-dose group，and the control group. The cardiac ultrasound was used to evaluate the structure and function of the rat heart. HE staining was used to observe the pathological changes of the rat myocardium. Transmission electron microscopy was used to observe myocardial autophagosomes. The expression of miR-30a and Beclin 1 mRNA in the rat myocardium was detected by RT-qPCR. Western Blot detected the expression of LC3-II/LC3-I and p62 protein. RESULTS: The network pharmacological analysis found that SMI could act synergistically through multiple targets and multiple pathways, which might exert a myocardial protective effect through PI3K-Akt signaling pathways and cancer microRNAs. In vivo, compared with the control group, the treatment group could improve the cardiac structure and function, and reduce myocardial pathological damage and the number of autophagosomes. The expression of miR-30a in the myocardium of rats in miR-30a agomir group and SMI group increased (P < 0.01)，Beclin 1 mRNA was decreased (P < 0.01)，LC3-Ⅱ/LC3-I protein was decreased (P < 0.01 or P < 0.05)，and p62 protein was increased (P < 0.01 or P < 0.05). CONCLUSIONS: SMI has the characteristics of multi-component, multi-target, and multi-pathway. It can inhibit myocardial excessive autophagy by regulating the expression of miR-30a/Beclin 1 and alleviate the myocardial injury induced by doxorubicin.
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Zhang et al. (2021) studied Doxorubicin cardiotoxicity. Shenmai Injection vs. Control group and model group was evaluated on Expression of miR-30a, Beclin 1 mRNA, LC3-II/LC3-I, and p62 protein (p=< 0.01). Shenmai Injection improved cardiac structure and function and inhibited excessive autophagy in a rat model of doxorubicin cardiotoxicity by increasing miR-30a and decreasing Beclin 1 mRNA (P<0.01).
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