The Protective Effect Of CEPO On The Myocardial Injury Caused By Epilepsy From KA

3Objective:Brain-heart syndrome is the result of brain diseases (epilepsy, cerebral hemorrhage, cerebral ischemia, subarachnoid hemorrhage, acute brain injury, brain tumor, intracranial inflammation, etc.) caused by nerve - humoral regulation dysfunction caused by similar to myocardial ischemia, arrhythmia, myocardial infarction or a group of symptoms of heart failure.In recent years ,the number of the reporte about brain-heart syndrome increased,intracranial brain disorders that can cause heart syndrome are reported in China, However, epilepsy which caused by amygdala lesions induced heart syndrome are rare clinical reports, MAPK as intracellular signal transduction system,which is important in the KA-induced seizure model and cardiovascular system , There is no clear conclusion about the role of MAPK in the course of brain-heart syndrome by epilepsy , Our purpose will address below:â‘ Whether the P38MAPK and JNKMAPK pathway caused Myocardial cell apoptosis in during the course of brain-heart syndrome by epilepsy which caused by KA ?â‘¡After treatment of EPO and CEPO,we detect the changes of cardiac myocyte apoptosis and induce whether by blocking the JNKMAPK and P38MAPK pathway about EPO and CEPO Mechanism of protecting cardiac myocytes? This will make more in-depth research.Methods:Our research use 120 male Wistar rats, weighted about 250 g,they were randomly divided into four groups: The control group (PBS group), model group (KA group), EPO group and CEPO group, each group was divided again into 0 hours, 2 hours, 6 hours, 12 hours and 24hours time point, each group has 6 rats.The expression of P38MAPK and JNKMAPK were detected by Immunohistochemical method on each time point,Using Image-Pro Plus image analysis software to determinate the myocardial tissue gray value of which expressed by P38MAPK and JNKMAPK, we use the flow cytometry technique to detect myocardial cell apoptosis and use the Electron microscope to observe myocardial on the most obvious expression point of P38MAPK and JNKMAPK. Results:The result of Immunohistochemical detection showed that the expression of P38MAPK and JNKMAPK begin increase since epilepsy attack, after 6 hours, the expression reach the top point and then gradually decline,there was significant difference between the PBS group and the KA group on 2h,6h and 12h(P<0.05), there was significant difference between the EPO group,CEPO group and the KA group on 2h,6h and 12h (P<0.05), but there was no significant difference between the EPO group,CEPO group,PBS group and the KA group on 0h and 24h (P>0.05).CEPO group exert protective effect on myocardial cell without affecting the red blood cell systems, After treatment of EPO and CEPO, compared with the KA group, the myocardial cell apoptosis of each group decreased markedly and the myocardial ultrastructure improved,those results show that epilepsy cause myocardial cell apoptosis through P38 and JNK signal pathways, EPO and CEPO can exert respective mechanisms of myocardial protection .Conclusion:1.The epilepsy models was made through inject KA in the right amygdala, the process of the model is easy, economical and effective, the epilepsy model have high success rate and high reproducibility;2.During the course of brain-heart syndrome by epilepsy which caused by KA, the expression of JNKMAPK and P38MAPK are begin increase since 0 hours, reach peak at 6 hours and follow gradual decline and at 24 hours close to normal in myocardial cells;3.CEPO can exert protective effects on myocardial under the circumstances that does not affect the red blood cell hyperplasia ; After treatment EPO and CEPO, the expression of JNKMAPK and P38MAPK decrease through their respective mechanisms of the signaling pathways in myocardial cells, this result can inhibit myocardial cell apoptosis which caused by Epilepsy and protect myocardial cell; that's indicate that the mechanism of EPO and CEPO inhibit JNKMAPK and P38MAPK is one of the mechanism of target organ protective effect.