Scutellarin ameliorates ischemia/reperfusion injury‑induced cardiomyocyte apoptosis and cardiac dysfunction via inhibition of the cGAS‑STING pathway

Ischemic heart disease is a common Cardiovascular Disease. Scutellarin (SCU) exhibits protective effects in ischemic cardiomyocytes; however, to the best of our knowledge, the protective mechanism of SCU remains unclear. The present study was performed to investigate the protective effect of SCU on cardiomyocytes after ischemia/reperfusion (I/R) injury and the underlying mechanism. Mice were intraperitoneally injected with SCU (20 mg/kg) for 7 days before establishing the heart I/R injury model. Cardiac function was detected using small animal echocardiography, apoptotic cells were visualized using TUNEL staining, the myocardial infarct area was assessed by 2,3,5-triphenyltetrazolium chloride staining, and the protein levels of Cyclic GMP-AMP Synthase (cGAS), stimulator of interferon genes (STING), Bcl-2, Bax and cleaved Caspase-3 were detected by western blotting. In in vitro experiments, H9c2 cells were pretreated with SCU, RU.521 (cGAS inhibitor) and H-151 (STING inhibitor), before cell hypoxia/reoxygenation (H/R) injury. The viability of H9c2 cells was detected using a Cell Counting Kit-8 assay, the rate of Apoptosis was determined by flow cytometry, and the protein expression levels of cGAS, STING, Bcl-2, Bax and cleaved Caspase-3 were detected by western blotting. It was revealed that SCU ameliorated cardiac dysfunction and Apoptosis, and inhibited the activation of the cGAS-STING and Bcl-2/Bax/Caspase-3 signaling pathways in I/R-injured mice. It was also observed that SCU significantly increased cell viability and decreased Apoptosis in H/R-induced H9c2 cells. Furthermore, H/R increased the expression levels of cGAS, STING and cleaved Caspase-3, and decreased the ratio of Bcl-2/Bax, which could be reversed by treatment with SCU, RU.521 and H-151. The present study demonstrated that the cGAS-STING signaling pathway may be involved in the regulation of the activation of the Bcl-2/Bax/Caspase-3 signaling pathway to mediate I/R-induced cardiomyocyte Apoptosis and cardiac dysfunction, which could be ameliorated by SCU treatment.

apoptosis; cyclic GMP-AMP synthase; ischemia/reperfusion injury; scutellarin; stimulator of interferon genes.