Exogenous hydrogen sulfide protects against high glucose‑induced apoptosis and oxidative stress by inhibiting the STAT3/HIF‑1α pathway in H9c2 cardiomyocytes

摘要: Hydrogen sulfide (H2S), an endogenous gasotransmitter, possesses multiple physiological and pharmacological properties including anti-apoptotic, anti-oxidative stress cardiac protective activities in diabetic cardiomyopathy. An increasing body of evidence has suggested that signal transducer activator transcription 3 (STAT3) beneficial effects the heart. However, effect diabetes on phosphorylation or activation STAT3 appears to be controversial. The present study was designed investigate precise function STAT3/hypoxia-inducible factor-1α (HIF-1α) signaling pathway high glucose (HG)-induced H9c2 cardiomyocyte injury STAT3/HIF-1α cardioprotective action H2S. results revealed GYY4137 pretreatment substantially ameliorated HG-induced decrease cell viability increase lactate dehydrogenase (LDH) release cells. Additionally, HG treatment resulted upregulation phosphorylated (p)-STAT3/STAT3 ratio HIF-1α protein expression cells, indicating induced by HG. inhibition transfection with small interfering (si)-RNA attenuated downregulation LDH release. Furthermore, siRNA combined apoptosis as illustrated number terminal deoxynucleotidyl transferase dUTP nick end labeling-positive caspase-3 activity, BCL2 associated X, regulator/BCL2 regulator In addition, blocked oxidative evidenced reactive oxygen species generation, malondialdehyde content NADPH oxidase 2 expression, superoxide dismutase activity glutathione level. Notably, reduce p-STAT3/STAT3 resulting HG-treated Altogether, demonstrated H2S mitigates damage, reduces suppressing pathway.