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The Effect Of Ischemia/reperfusion On The Expression Of P-selectin Of The Rat And The Role Of MgS04

Posted on:2002-07-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:S Q YingFull Text:PDF
GTID:1104360062985656Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Myocardial injury of ischemia/reperfusion(I/R) often occurs after thrombolysis and PTCA in patients with acute myocardial infarction,extracorporeal circulation and transplantation of the heart and so on. Such injury is involved with aggregation of platelets,infiltration of leukocytes,intracellular overload of calcium,burst of oxygen free radicals and so on. While P-selectin ( Ps ) ,which is the marker of activated platelets and injuried endothelial cells(ECs) ,acts as an intermediator of these factors. It is demonstrated that expressions of Ps on ECs,platelets as well as the expression of intergrin CD lib on leukocytes can promote to interact between polymorphonuclear(PMN)/monocyte and ECs/platelets,which may form no reflowing phenomenon and induce leukocytes to flow out of blood vessels and enter into myocardial tissues where they release inflammatory factors,cytokines and so on ,which result in injury of myocardium. The abnormal expressions of Ps mRNA . MCP-1 mRNA in myocardial tissue are considered to be an important pathophysiological mechanism for some heart diseases. Recently the function of Mg2+ on the heart gains more and more attention. As a natural antagonistor of Ca2+, Mg2+ can prevent intracellular overload of Ca2+ in addition to inhibiting the expression of Ps , which indicates Mg2* has a protective role in the injury of I/R of myocardium by affecting the expressions of the cell adhesion molecules(CAMs) . In this project, to study the pathophysiological mechanism of I/R injury and the protective role of MgSO4 in this respect, we set up the I/R model of the whole Sprague Dawley(SD) rat . Basing on monitoring arrhythmia by ECG monitor , measuring the concentration Mg2+ and Ca2+ in blood serum by the method of the ion-selective electrode and observing the myocardial structure of left ventricle under the light microscope,the expression of Ps on ECs was measured by ELISA ,while the expressions of Ps onplatelets , CD lib on leukocytes and the expressions of Ps mRNA ,MCP-1 mRNA in myocardial tissue were measured with flow cytometer and RT-PCR respectively, and these indexes were also measured after the administration of MgSO4.Part 1 The effects of ischemia/reperfusion on the expression of P-selectin of the endothelial cells and the cardiac impairment of rats as well as the role of MgSO4: I/R can give rise to reperfusion arrhythmia,injury of endothelium of bloodvessel,necrosis of myocardium and inflammation of myocardial interstice.This study was designed to evaluate the effect of I/R on the expression of Ps of the endothelial cells and the cardiac impairment of SD rats as well as the protective role of MgSO4 .Methods: All 96 SD rats were divided into four groups.Group A (control group ):6 animals without any procedure as a control group; Group B(sham group,totally 30 rats): the same procedures as Group C except that the tourniquet of anterior descending artery(LAD) of coronary artery remained loose all the time;Group C(I/R group) :myocardial ischemia was caused by ligation of the root of LAD of the coronary artery;for 45 mins after coronary occlusion,the tourniquet was loosed to recover blood supply for 5 mins* 30mins. 60minSx ISOmins* 360mins (recorded to R5. R30> R6CK R180, R360 for short respectively, 6 rats at each timepoint, totally 30 ones ); Group D ( Mg2+ group,totally 30 ones ): the same procedures as Group C except the application of MgSO4 from 30 mins before procedure to after immediate reperfusion. Arrhythmia was monitored by ECG monitor , the concentration of Mg2+ and Ca2+ in serum was measured with the method of the ion-selective electrode,expression of Ps on ECs was detected with immunohistochemistry, and the pathological changes of myocardial tissue of the left ventricle was observed under the light microscope.Results:1 The ventricular arrhythmic score(VAS) of Group A was 1.33?. 51, while there was no significant difference between the VAS of Group B at any timepoint of reperfusion and that of Group A;the VAS of Group C at any timepoint of reperfusion was...
Keywords/Search Tags:ischemia, reperfusion, injury, ventricular arrhythmia, necrosis of myocardium, P-selectin, CD11b, MCP-1, Ca2+, Mg2+
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