Remifentanil preconditioning confers cardioprotection via c-Jun NH 2 -terminal kinases and extracellular signal regulated kinases pathways in ex-vivo failing rat heart

摘要: Abstract Remifentanil preconditioning (RPC) exerts protection in normal hearts, but has not been investigated heart failure. The aim of the present study was to evaluate effect RPC a chronic failing rat model and mechanisms involving mitogen-activated protein kinases (MAPK) Bcl-2 family. doxorubicin induced hearts were subjected 30 min ischemia / 120 min reperfusion (IR) with or without by using Langendorff apparatus. three cycles 5 min remifentanil drug-free perfusion before IR, different concentrations: 25, 50 100 μg/l. An extracellular signal regulated (ERK) inhibitor PD98059, p38MAPK SB203580, c-Jun NH2-terminal (JNK) SP600125 perfused at 10 min RPC. Infarct size, cardiac function kinase activity determined. significantly reduced infarct size rise lactate dehydrogenase (LDH) level caused IR injury heart. JNK ERK PD98059 abolished mediated reduction on LDH after reperfusion. In addition, increased phosphorylation JNK, ERK1/2 downstream GSK-3β, as well Bcl-2/Bax ratio, while, these changes completely reversed PD98059. And note, SB203580 had no effect. conclusion, our results suggested that activation pathways, leading inhibition GSK-3β regulating family, is major mechanism confers cardioprotection