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Reduced cardiac ischemia/reperfusion injury by hypothermic reperfusion via activation of transient receptor potential M8 channel

Author:
Cheng, Quan-yi, Yang, Meng-cheng, Wu, Jing, Jia, Xiao-li, Xiao, Chao, Lian, Ting, Zhang, Shi-zhong
Source:
Life sciences 2019 v.232 pp. 116658
ISSN:
0024-3205
Subject:
antagonists, apoptosis, cardiomyocytes, cardioprotective effect, caspase-3, infarction, laboratory animals, lactate dehydrogenase, malondialdehyde, messenger RNA, myocardial ischemia, quantitative polymerase chain reaction, rats, reperfusion injury, signal transduction, superoxide dismutase
Abstract:
To investigate the cardioprotective effects of hypothermic (25 °C) reperfusion on ischemia/reperfusion injury and the role of transient potential channel M8 (TRPM8) in this process.Western blot and real-time PCR were used to monitor the expression of TRPM8 in myocardium. Myocardial ischemia/reperfusion injury was induced by 30 min of global ischemia followed by 120 min of reperfusion in Langendorff-perfused hearts from Sprague-Dawley rats. The reperfusion was either normothermic (37 °C) or hypothermic (25 °C). Infarct size and left ventricular function were assessed, and lactate dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA) in the coronary effluent were measured spectrophotometrically, and cardiomyocyte apoptosis was detected by TUNEL assay. The expression of TRPM8, Bcl-2, Bax, cleaved capspase-3, RhoA, and ROCK2 was quantified.TRPM8 protein and mRNA were expressed in rat myocardium. Hypothermic reperfusion decreased the infarct size, LDH activity, MDA content, apoptosis, and expression of Bax, cleaved caspase-3, RhoA, and ROCK2 compared with normothermic reperfusion. These effects were associated with improved recovery of left ventricular contractility, and were reduced by BCTC, a TRPM8 antagonist. Ischemia/reperfusion injury and the increased expression of Bax, caspase-3, RhoA, and ROCK2 induced by normothermic reperfusion were reduced by Icilin, a TRPM8 agonist.Hypothermic reperfusion at 25 °C has cardioprotective effects against ischemia/reperfusion injury via activation of TRPM8 to inhibit the oxidative stress-related RhoA/ROCK2 signal pathway.
Agid:
6536536