Effects of dexmedetomidine postconditioning on myocardial ischemia and the role of the PI3K/Akt-dependent signaling pathway in reperfusion injury

Abstract

The present study aimed to determine whether post-ischemic treatment with dexmedetomidine (DEX) protected the heart against acute myocardial ischemia/reperfusion (I/R)-induced injury in rats. The phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)-dependent signaling pathway was also investigated. Male Sprague Dawley rats (n=64) were subjected to ligation of the left anterior descending artery (LAD), which produced ischemia for 25 min, followed by reperfusion. Following LAD ligation, rats were treated with DEX (5, 10 and 20 µg/kg) or underwent post-ischemic conditioning, which included three cycles of ischemic insult. In order to determine the role of the PI3K/Akt signaling pathway, wortmannin (Wort), a PI3K inhibitor, was used to treat a group of rats that had also been treated with DEX (20 µg/kg). Post-reperfusion, lactate dehydrogenase (LDH), cardiac troponin I (cTnI), creatine kinase isoenzymes (CK-MB), superoxide dismutase (SOD) and malondialdehyde (MDA) serum levels were measured using an ultraviolet spectrophotometer. The protein expression levels of phosphorylated (p)-Akt, Ser9-p-glycogen synthase kinase-3β (p-GSK-3β) and cleaved caspase-3 were detected in heart tissue by western blotting. The mRNA expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected using reverse transcription-polymerase chain reaction. At the end of the experiment, the hearts were removed and perfused in an isolated perfusion heart apparatus with Evans blue (1%) in order to determine the non-ischemic areas. The risk and infarct areas of the heart were not dyed. As expected, I/R induced myocardial infarction, as determined by the increased serum levels of cTnI, CK-MB and MDA, and the decreased levels of SOD. Post-ischemic treatment with DEX increased the expression levels of p-Akt and p-GSK-3β, whereas caspase-3 expression was reduced following DEX treatment compared with in the I/R group. Compared with the I/R group, the ratio of Bcl-2/Bax at the mRNA level was elevated in the DEX and ischemic post-conditioning groups, whereas the expression levels of Bax were decreased. Conversely, the effects of DEX were attenuated by Wort. These results indicated that, similar to post-ischemic conditioning, post-ischemic treatment with DEX protects the heart against I/R via the PI3K/Akt-dependent signaling pathway, possibly by activating GSK-3β.

Effects of dexmedetomidine post‑treatment on BDNF and VEGF expression following cerebral ischemia/reperfusion injury in rats

“…In addition, VEGF was revealed to regulate the PI3K/Akt signaling to inhibit the activity of Caspase-3 and to regulate voltage-gated potassium channels, thereby, reducing ischemia-induced neuronal death. DEX post-treatment was reported to be beneficial to neuroprotection by activating PI3K/Akt signaling pathway (17). The present study aimed to further explore whether the post-treatment with DEX increased the expression levels of BDNF and VEGF following ischemia/reperfusion (I/R) injury.…”

Dexmedetomidine alleviates cisplatin‑induced acute kidney injury by attenuating endoplasmic reticulum stress‑induced apoptosis via the α2AR/PI3K/AKT pathway

“…However, the molecular mechanisms underlying the effects of dex against cP-induced aKi have not been fully elucidated. as the pathogenesis of cP-induced aKi is mediated by erS-induced apoptosis, dex may be able to alleviate apoptosis by inhibiting erS (27,28). Therefore, the present study aimed to investigate the protective effects of dex against cP-induced aKi and assessed whether these effects were mediated by attenuation of erS-induced apoptosis via the α 2 ar/Pi3K/aKT pathway.…”

Dexmedetomidine Postconditioning Alleviates Hypoxia/Reoxygenation Injury in Senescent Myocardial Cells by Regulating lncRNA H19 and m6A Modification

“…As such, it is widely used as anesthesia for cardiovascular surgery; indeed, perioperative Dex reportedly reduces the mortality rate at 1 year after surgery, as well as the incidence of postoperative complications and delirium following cardiac surgery [7]. In animal experiments, ischemic postconditioning with Dex reduced the infarct area of adult rat hearts and expression of lactate dehydrogenase, creatine kinase isoenzymes, and malondialdehyde [8]. Although a number of new cardioprotective therapies have been discovered in the research laboratory, only a few of these have been demonstrated to improve clinical outcomes [9].…”