title: 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.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.
authors.forename: Xiang Yang
authors.initials: XY
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Gu
authors.affiliation: Department of Physiology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Physiology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Qiao Feng
authors.initials: QF
authors.lastname: Zong
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015415:Biomarkers; D002316:Cardiotonic Agents / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D057775:Ischemic Postconditioning / Q000379:methods; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002316:Cardiotonic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D020927:Dexmedetomidine; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D052279:Creatine Kinase, MB Form; D053148:Caspase 3