Propofol postconditioning alleviates diabetic myocardial ischemia‑reperfusion injury via the miR‑200c‑3p/AdipoR2/STAT3 signaling pathway

Abstract

Myocardial ischemia/reperfusion (Mi/ri) syndrome is one of the leading causes of mortality and disability. Propofol postconditioning is known to improve myocardial ischemia/reperfusion injury (Mi/ri). The present study aimed to explore the mechanism of propofol postconditioning in diabetic Mi/ri. diabetic Mi/ri rat models were established and the rats were treated via propofol postconditioning. Staining with 2,3,5-triphenyl-2H-tetrazolium chloride, H&e staining, Tunel staining and eliSa were applied to detect infarct size, pathological changes, apoptosis and oxidative stress-related factor and apoptotic factor levels, respectively. Subsequently, the effect of propofol on H9c2 cells was also assessed using the cell counting Kit-8 assay. High-glucose hypoxia/reperfusion (H/r) models of H9c2 cardiomyocytes were established. mir-200c-3p overexpression or adipor2 silencing combined with propofol postconditioning was performed in H/r-induced H9c2 cells and STaT3 protein expression levels were determined. Propofol postconditioning significantly reduced myocardial infarct size, oxidative stress and apoptosis in diabetic Mi/ri models. Furthermore, propofol postconditioning significantly reduced the oxidative stress and apoptosis of H9c2 cells in high-glucose H/r models. Propofol postconditioning also significantly downregulated miR-200c-3p expression levels and promoted adipor2 expression levels. mir-200c-3p overexpression or AdipoR2 downregulation significantly reversed the effects of propofol postconditioning on its antioxidation and anti-apoptotic effects in H9c2 cells and on decreasing STaT3 phosphorylation levels. Together, the results of the present study demonstrated that propofol postconditioning inhibited mir-200c-3p, upregulated adipor2 and activated the STaT3 signaling pathway, thus alleviating diabetic Mi/ri and therefore highlighting its potential as a treatment of diabetic Mi/ri.

Dexmedetomidine combined with propofol attenuates myocardial ischemia/reperfusion injury by activating the AMPK signaling pathway

“…MDA is a remarkable factor produced by OS, while SOD is a key antioxidant enzyme. Previous studies have presented that Dex can ease OS reactions and stress responses and PPF can inhibit the production of OS-related factors[ 43 , 44 ]. Our results showed that the combination of Dex and PPF better inhibited OS were used alone.…”

The crosstalk between STAT3 and microRNA in cardiac diseases and protection

“…MiR-421 directly targets toll-like receptor 4 (TLR4), which is the upstream of the JAK2/STAT3 signaling pathway in inflammation in I/R injury ( 28 ). MiR-200c-3p directly targets at adiponectin receptor 2 (AdipoR2), which activated the STAT3 signaling pathway to suppress apoptosis in I/R ( 29 ). Fourth, STAT3 is the indirect target of miRNA to reduce the phosphorylation of STAT3.…”