Dissertation > Excellent graduate degree dissertation topics show

The Protective Effects of Erythropoietin on Myocardial Ischemia-reperfusion Injury

Author: GaoMingYu
Tutor: QiGuoXian
School: China Medical University
Course: Internal Medicine
Keywords: erythropoietin (EPO) ischemia reperfusion injury (IRI) TNF-α IL-6 NF-κB HIF-1α Akt
CLC: R541
Type: PhD thesis
Year: 2007
Downloads: 273
Quote: 0
Read: Download Dissertation

Abstract


ObjectivesPercutaneous coronary intervention(PCI)has already been the main mechanism in the therapy of myocardial infarction,since then ischemia reperfusion injury(IRI) associated with percutaneous coronary intervention(PCI)also became the hot issue in research region.With the in-depth understanding of erythropoietin(EPO),EPO is administered in sufficient amount can protect cardiac myocytes from ischemic reperfusion injury.Currently,only animal can be used in the study and ligation of coronary artery is the base of the IRI model establishment.The first part of this study is going to establish IRI model by coronary occlusion through saccule intervention.This model is more similar to the clinical therapy of PCI in myocardial infarction.Based on this to detect ventricular arrhythmia,left ventricular function,myocardial cells death markers and myocardial infarct area after IRI and observe the protective role of EPO from IRI.With the in-depth research in cardiac myocyte ischemia reperfusion injury(IRI), more and more evidences showed that the inflammation mainly caused by neutrophils may play prominent roles in the pathogenesis of ischemia-reperfusion injury(IRI). TNF-αand IL-6 are important mediators of inflammation.The past researches showed that the nuclear factor-kappa B(NF-κB)can regulate the previous two genes in the inflammation.In the course of myocardial ischemia/reperfusion injury,angiogenesis and and promotion of branch circulation as to increase the coronary reserve are also important to protect myocardium from injury.Hypoxia-inducible factor-1(HIF-1)plays key roles in angiogenesis under hypoxia condition by regulating expressions of other growth factors.Under the hypoxia situation,the expression of HIF-1αincreased significantly.Protein kinase B(Akt)can also up-regulate HIF-1αexpression.Many studies have comfirmed that EPO can promote the proliferation of endothelial cells under endocardium.The other part of this study is to establish IRI model in rats to observe the effects of EPO on inflammation factors and HIF-1αafter myocardium IRI and to discuss the possible mechanism.MethodsThe first part1、A total of 40 pigs were divided into four groups:sham-operation group,IRI group,EPO-treated group after ischemia(EPO-1)and EPO-treated group after reperfusion(EPO-2).IRI model was established by occluding the anterior descending branch of coronary artery.The pigs in EPO-1 group received erythropoietin(EPO) 5000 units/kg injected subcutaneously through belly at the time of occlusion,the pigs in EPO-2 group received the same dose injection subcutaneously through belly at the time of occlusion released.2、And then make a record of the kinetic parameter of blood flowing,LVSP, LVEDP,dp/dtmax and dp/dtmin for 120 minutes reperfusion.3、Make a record of ventricular arrhythmia.4、And detect the CK and LDH levels respectively for 120 minutes reperfusion.5、Take out the heart and calculate the ratio of left ventricular infarct area to the quality of left ventricular.The second and third part1、A total of 40 male Wistar rats were randomly divided into sham-operation group, IRI group,EPO-treated group after ischemia(EPO-1)and EPO-treated group after reperfusion(EPO-2).Establishment of the model is through ligating the anterior descending branch of coronary artery.The rats in EPO-1 received erythropoietin(EPO) 5000 units/kg injected subcutaneously on belly at the time of ligation,the rats in EPO-2 received the same injection subcutaneously on belly at the time of ligation released.2、Collected vein blood for 120 minutes Reperfusion and detected TNF-α、IL-6 by ELISA assay.3、Killed the rats and took out the hearts,detected the expression of NF-κB、HIF-1αand Akt protein in myocardium by Western blots and the expression of HIF-1αmRNA in myocardium tissue by RT-PCR assay.ResultsThe first part1、Compared to the sham-operation group,all the indexes of IRI group significantly changed(P<0.01).2、Compared to IRI group,blood engorging speed(p<0.01),left ventricular contractive and diastoling function(p<0.05)showed significant increase after reperfusion pretreated with Epo;however,both myocardial cells necrosis markers (p<0.01)levels and myocardial infarct area(p<0.05)significantly reduced.3、Compared to EPO-2,EPO-1 showed much lower myocardial cells necrosis levels and myocardial infarction areas,the difference is significant(P<0.05).The second part1、Compared to the sham-operation group,IRI group showed increased expression of TNF-α,IL-6 and NF-κB significantly(P<0.01).2、Compared to IRI group,groups pretreated with Epo demonstrated that expression of TNF-α、IL-6 and NF-κB decreased significantly(P<0.01).3、Expression of TNF-α、IL-6 and NF-κB was lower in EPO-1 than EPO-2(P<0.05).4、The expression of NF-κB and TNF-α,IL-6 showed direct correlation.The third part1、Compared to the sham-operation group,the expression of HIF-1αin IRI group significantly increased(P<0.01),but Akt expression had no significant change(P>0.05).2、Compared to IRI group,the expression of HIF-1αand Akt increased significantly in Epo pretreated groups(P<0.01).3、Compared to EPO-2,the expression of HIF-1αand Akt had more significant increase in EPO-1(P<0.05).4、HIF-1αand Akt are positive correlated.Conclusion1、EPO-treatment is effective in reducing ventricular arrhythmia,improvement of left ventricular function,decreasing myocardial infarction marker levels and myocardial infarction area.2、In aspects of decreasing myocardial infarction marker levels and myocardial infarction area,the effectiveness of EPO-treatment at the time of ischemia is much better than at the time of reperfusion,which suggests that Epo treatment in early ischemia phase may be more effective in protection of myocardial cells.3、EPO treatment can reduce the serum level of TNF-αand IL-6 to play a protective role from IRI by reducing expreesion of NF-κB pathway.4、The effectiveness of EPO-treatment administrated at the time of ischemia is much better than at the time of reperfusion.5、EPO treatment can play protective role by increasing HIF-1αand Akt expression after IRI.6、The effectiveness of EPO-treatment administrated at the time of ischemia is much better than at the time of reperfusion.

Related Dissertations

  1. Inhibition of RAW264.7 Macrophage Inflammatory Cytokines Release by Guggulsterone,R285
  2. Infectious Bursal Disease Virus Particle Vaccine Research and Its Immune Efficacy Evaluation,S858.31
  3. The Effects of PCV2 on NF-κB Signal in Piglet’s Lymphocytes in Vitro,S858.28
  4. Roles of MMP-7 and Lysozyme in the Pathogenesis of Ulcerative Colitis Induced by DSS in Balb/c Mice,S858.91
  5. Preparation of Monoclonal Antibody to Porcine TNF-α and Expression of TNF-α in PAM Infected with PRRSV,S858.28
  6. Live alone the study of parasitic soup rabbit lumbar disc herniation model in vivo tumor necrosis factor in rats,R285.5
  7. Nuclear Dot Protein NDP52 Bind to Tumor Necrosis Factor Receptor Associated Factor 6 and Their Clinical Significance of Research,R363
  8. Effective of the Interaction between NDP52 and TRAF6 and TRAFs on NF-κB Signal Pathway,R363
  9. The Molecular Mechanism Intervention of Selenium on the Learning and Memory Injury by Drinking Water Fluorosis,R599
  10. The Effect and Mechanism of p38MAPK Inhibitor CBS3830 on Intimal Hyperplasia in Autogenous Vein Grafts of Diabetic Rats,R587.1
  11. The Expression and Significance of Nuclear Factor Kappa B (NF-κb) and IL-6 in the Degenerated Cervical Intervertebral Disc,R681.55
  12. Effects of Partial Hepatic Ischemia/Reperfusion Injury on Postoperative Cognitive Function in Mice,R614
  13. Cysteamine on T Lymphocyte Proliferation in Post-Operation Goats and Its Mechanism Underlying,S858.27
  14. Cloning, Expression and Bioactivity Analysis of Goat Interleukin-1β and Interleukin-6,S827
  15. Meridians of Asthma Thread Burying Model Rats IL-4 Such Impact Experimental Study,R245
  16. Role of G31P in Smooth Muscle Migration of A7r5 Cells Induced by Interleukin-8,R363
  17. Experimental Study of Influence of Atrovastatin on Expression of NF-κB in Retionpathy of Diabetic Rats,R587.1
  18. Expression and Significance of HIF-1α on the Insulin Resistance during the Injury of Reperfusion of Ischemic Myocardium in Dog Undergoing Cardiopulmonary Bypass,R654.1
  19. The Expression and Mechanism of NF-κ B and IL-6 after 90% Portal Vein Ligation in Rats,R657.3
  20. The Sequence Analysis of RNA Components from Lactobacillus Metabolites and Parts of the Biological Function,R378
  21. Noble Dendrobium Polysaccharides Attenuate Learning and Memory Deficits Induced by Lipopolysaccharide and Its Mechanisms in Rats,R285.5

CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease
© 2012 www.DissertationTopic.Net  Mobile