The IMD Intervention Research Of NF-KB And The Left Ventricular Remodeling

Objective1. Successfully produced animal models of myocardial infarction is aimportant means of the pathophysiological changes of myocardial infarction and treatment[15].Myocardial infarction which was caused by coronary artery ligation is conform with theclinical and pathological features, it is an ideal animal model of myocardial infarction. Thefirst part of the purpose of this subject is to investigate the preparation of rat myocardialinfarction model.2. Nuclear factor-kappa B （NF-kappa B） is binded with a variety promoteror enhance of gene of the κB sites and can promote transcription of gene. NF-κB signalingpathway of the IKK/IκB/NF-κB plays an important role in ventricular remodeling aftermyocardial infarction and the pathophysiological process of heart failure. Intermedin （IMD）is the Inhibitors of nuclear factor-κB protein （IκB）,which can inhibit protein kinase （IKK）activation，and thus indirectly inhibit NF-κB signaling pathway. The second part of thissubject with acute myocardial infarction in rats for the study is observate the expression ofNF-κB in the myocardium after acute myocardial infarction and intervention of IMD aboutNF-kB and right ventricular remodeling.Methods1. thirty rats were randomly divided into2groups: sham group accepted shamoperation, while MI model group received the ligation of left anterior descending artery. Andall groups recorded the electrocardiogram before and after surgery. Ultrasonic heartbeatgraph were detected4weeks post operation.2.Ligation of the rat left anterior descending coronary artery myocardial infarction model preparation and divided into3groups: shamgroup,MI model group and IMD group. then cardiac index in model rats was measured: leftventricular end diastolic diameter and left ventricular end systolic diameter were determinedby Ultrasonic heartbeat graph, Monitoring of hemodynamic parameters (including heart rate（HR）, left ventricular end-diastolic pressure （LVEDP） and left ventricular systolic pressure（LVSP）, NF-κB and IκB protein evaluated by Western blot，myocardial levels of MMP2and MMP₉activity is measured by Gelatin zymography; after AMI in rats venous plasmabrain natriureticpeptide（BNP） levels is measured by ELISA,histopathological analysis.Results1. Left ventricular end diastolic diameter and Left ventricular end systolicdiameter increased （p<0.05或0.01） in MI model group compared with sharp group.significantly Visual observation showed there existed the myocardial infarction only in MImodel group, with the achievement rate being83.3%, and it had not the myocardial infarctionin sharp group.2. Left ventricular end diastolic diameter and Left ventricular end systolicdiameter increased （p<0.05或0.01） in MI model group compared with sharp group and theintervention group. Compared with control group, NF-κB protein levels were higher not onlyin myocardial tissues but also in cardiocytes of IM groups, as well as IκB protein levels werereduced. But those can be attenuated by IMD,MMP2and MMP9activity was significantlydecreased，rat venous plasma BNP is significantly reduced.Conclusion1. This experiment provided an easy way to establish the MI model，which was reproducible and credible. The changes of general morphological and ECG andechocardiography is a sign of success.2.NF-κB protein levels were significantly higher incardiocytes of IM groups.3. NF-κB protein levels can be attenuated by IMD.4. IMD mayreverse the myocardial remodeling through blocking NF-κB.