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

Li,Jiu-Kang; Song,Zhi-Ping; Hou,Xing-Zhi

doi:10.3892/etm.2023.11854

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

Authors:
- Jiu-Kang Li
- Zhi-Ping Song
- Xing-Zhi Hou
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Affiliations: Department of Infectious Diseases, The People's Hospital of Yue Chi County, Guang'an, Sichuan 638300, P.R. China, Department of Cardiovascular Medicine, The People's Hospital of Yue Chi County, Guang'an, Sichuan 638300, P.R. China
Published online on: February 17, 2023 https://doi.org/10.3892/etm.2023.11854
Article Number: 155
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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