Role Of JAK/STAT Pathway In Regulating Myocardial Damage At Early Stage After Ischemia-reperfusion Injury

As the beginning of modern cardiac surgery and essential technique for cardiac operation, extracorporeal circulation is often accompanied with ischemia-reperfusion injury and systemic inflammatory reaction that act with each other at the early stage of etracorporeal circulation and are beyond effective treatment. There are many signal pathways for cell response. Blockade of the key signal pathway could effectively decrease or eliminate cell effect induced by stimulating factors. As an important signal transducing pathway, the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is activated by various cytokines and growth factors. The JAK/STAT pathway plays an important role in growth, proliferation, differentiation, inflammation and apoptosis of cells. More and more studies have concentrated on the role of the JAK/STAT pathway in pathogenesis of cardiac disease, ie, the JAK/STAT pathway is closely related with myocardial hypertrophy, cardiac failure, cardioprotection induced by ischemic preconditioning as well as cardiac dysfunction induced by ischemia-reperfusion. We assumed that the JAK/STAT pathway may correlate with cardiac damage caused by ischemia-reperfusion and inflammatory factors.Objective: The purpose of this study is to clarify the difference between signal pathways of JAK/STAT and NF-κB, MAPK, PKC and Ca2+ in myocardium damage induced by ischemia/reperfusion, investigate if JAK1, JAK2, STAT1, STAT3 in myocardium are activated after ischemia-reperfusion, identify the role of the activated JAK/STAT in myocardium damage induced by ischemia/reperfusion and investigate the mechanisms of JAK/STAT signal pathway causing myocardium damage.Methods: Immature rat ventricular myocytes were cultured and an isolated rat working heart model established. The study was consisted of two parts. In the first part, the cultured immature rat cardiomyocytes were randomly divided into 9 groups including control group, ischemia-reperfusion group. AG490 pretreatment group, RPM pretreatment group, AG490+RPM pretreatment group, PDTC pretreatment group, SB203580 pretreatment group,...