The Regulation Of Nuclear Factor-κ B On The Cardiac Myocyte Apoptosis Influenced By Ischemic Preconditioning

The evidences from some recent reseach conformed the concurrence of both necrosisand apoptosis in myocardium during ischemia and reperfusion., which suggests that apoptosismay be an important pathological character of ischemic and reperfusion injury relatedmyocardial cell death as well. However, previous studies on myocardial apoptosis mainlyfocused on acute cardiac ischemia followed by occlusion of coronary artery, and theinfluences of cardiopulmonary bypass (CPB) on apoptosis of myocyte and it's time courseare not fully understood. Ischemic preconditioning (IPC) is the phenomenon whereby briefepisodes of ischemia protect the heart against a subsequent ischemic stress. As a endogenousprotective mechanism, it has been proved effective in a number of studies on reduction ofmyocardial necrosis in acute ischemic myocardium, but the effect of IPC onischemia/reperfusion myocardial apoptosis still kept uncertain. Moreover, the mechanism ofIPC on myocardial apoptosis during CPB has not been reported by now. It has recently beenconfirmed from foreign researches that the transcription factor nuclear factor-кB( NF-кB)may play a pivotal role in the myocardial ischemia/reperfusion(IR) injury. NF-кB is aredox-sensitive transcription factor involved in transcription of proteins in response tomutagenic, oxidative, and hypoxic stress. Under normal physiologic conditions, NF-кB isheld inactive in the cytoplasm by inhibitory subunit, IкB. Under confitions of oxidativestress, NF-кB disassociates from IкB, and translocates to the nucleus, where it initiates thetranscription of proinflammatory, procogulant, and vasoactive genes. NF-кB maybe play anessential role in the myocardial IR injury. Based on that mentioned above, a stable goat CPB model of IPC was designed in thestudy, and apoptosis of myocardial cell was detected using methods aimed at differentfeatures of apoptosis including alternations of cell ultrastructure, biochemical characters, andthe influences of IPC on it during CPB were observed. Furthermore, in order to evaluate the 5第二军医大学 英文摘要 硕士学位论文role of nuclear factor-кB(NF-кB)in the effect of IPC on myocardial apoptosis and discussthe mechanisms involved in, the inhibitor(Proline Dithitocarbamate, ProDTC)of NF-кBwas used. The main methods and results are described as follows: Twenty goats were randomly divided into four groups: group A (n=5, CPB group), groupB (IR group, n=5), group C (IPC group, n=5) and group D (IPC+ProDTC group n=5). Ingroup A, CPB was conducted without aortic cross-clamping (ACC); In group B, afterparalleling CPB for 45 min, goat hearts were subjected to 60 minutes of global ischemia,concomitantly 90 minutes of reperfusion. In IPC group, 3 cycles of 5 min of aorticcross-clamping (ACC) and 5 min of aortic unclamping were applied before goat hearts wereadapted for 15 min and followed by IR mentioned above. the inhibitor team goats wereadministered with ProDTC before and in IPC and same with group C in other aspects, thenthe experiments were made as follows.1.Establishment of goat cardiopulmonary bypass (CPB) model and studies onpathological alterations of myocardium and cardiac fuction during CPB. 1.1 Cardiac performance In group A, MAP, Dp/dt min and dp/dt max was not significantly different from thatbefore CPB(P>0.05). Dp/dt min and dp/dt max decreased during early reperfusion periods ingroup B, C and D, and better recovery of which were observed in group C compared to groupB and D(P<0.05). Then at 90 min after reperfusion in group C there was no significantdifference from group A(P>0.05). 1.2 Cardiac myocyte patholog and ultrastructure The ischemic and denaturation changes of myocardium were evaluated by the modifiedhaematoxylin fuchsin basic picric acid(HBFP) special pathologic staining. Diffuse HBFPstaining were observed in myocardium of IR group. How...