Abstract
Icariside II (ICS II) has been reported to have protective effects against oxidative stress. However, whether ICS II protects cardiomyocytes from myocardial infarction (MI), and the associated underlying mechanisms, remain to be elucidated. Therefore, the current study investigated the effects of ICS II on hypoxia‑injured H9c2 cells, as well as the associated molecular mechanisms. A hypoxic injury model was established to emulate the effects of MI. The effects of ICS II on the proliferation of rat cardiomyocyte H9c2 cells were assessed with cell counting kit‑8 assays. The apoptotic status of the cells was assessed by flow cytometry, and the expression of apoptosis‑related proteins was analyzed by western blotting. A microRNA (miRNA/miR) microarray was used to quantify the differential expression of miRNAs after ICS II treatment, and the levels of miR‑7‑5p were further quantified by reverse transcription‑quantitative PCR. Whether ICS II affected hypoxia‑injured cells via miR‑7‑5p was subsequently examined, and the target of miR‑7‑5p was also investigated by bioinformatics analysis and luciferase reporter assays. The effects of ICS II on the PI3K/Akt pathway were then evaluated by western blot analysis. Hypoxia treatment decreased viability and the migration and invasion abilities of H9c2 cells, and also induced apoptosis. ICS II significantly increased viability and reduced hypoxia‑associated apoptosis. Moreover, ICS II treatment led to the upregulation of miR‑7‑5p, and the protective effects of ICS II were found to rely on miR‑7‑5p. Moreover, BTG anti‑proliferation factor (BTG2) was identified as a direct target of miR‑7‑5p, and overexpression of BTG2 inhibited the protective effects of miR‑7‑5p. Finally, ICS II treatment resulted in the activation of the PI3K/Akt signaling pathway, which is essential for the survival of H9c2 cells under hypoxic conditions. In summary, ICS II reduces hypoxic injury in H9c2 cells via the miR‑7‑5p/BTG2 axis and activation of the PI3K/Akt signaling pathway.