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Proteomic Study on Protective Mechanism of Ischemic Preconditioning to the Lung Ischemia-reperfusion Injury

Author: WuLuQing
Tutor: ZhangChunFang
School: Central South University
Course: Surgery
Keywords: Ischemic preconditioning Ischemia-reperfusion injury Mass Spectrometry Two-dimensional gel electrophoresis Proteomics
CLC: R363
Type: Master's thesis
Year: 2008
Downloads: 114
Quote: 0
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Abstract


Ischemic preconditioning pretreated with one or more brief episodes of ischemia to enhance tolerance or adaptability of the organization of the subsequent prolonged ischemia-reperfusion injury. Ischemia-reperfusion injury is common in the dredge microcirculation in shock mitigation of coronary artery spasm, cardiovascular and cerebrovascular embolic recanalization, heart and lung after surgery and cardiac arrest, cardiopulmonary cerebral resuscitation, the amputated limb, organ transplantation and blood for recovery , is one of the major cause of subsequent organ dysfunction. A large number of studies have shown that ischemic preconditioning can significantly reduce subsequent ischemia-reperfusion injury. Lung ischemia-reperfusion injury is more common in open heart surgery, pulmonary artery sleeve resection, lung transplantation and occluding the pulmonary artery to lobectomy restore adverse effects on pulmonary function, and may be caused by surgery complications affect the prognosis. Lung ischemic preconditioning prevention and treatment of lung ischemia-reperfusion injury is the most effective measures, but the exact protection mechanism has not been elucidated. Studies have shown that, compared to ischemic preconditioning lung tissue, lung tissue not ischemic preconditioning, after subsequent prolonged ischemia and reperfusion, showed better ischemic tolerance and reperfusion resistance sexual leukocyte infiltration, pulmonary edema, local hemorrhage and alveolar rupture were significantly reduced, the cell structure, homeostasis, microcirculatory perfusion, energy metabolism, tissue function and genetic recombination has better continuity and recovery capacity. Majority of scientists from animal experiments and clinical trials on lung ischemic preconditioning lung protection mechanism fruitful research found that adenosine, bradykinin, arachidonic acid metabolites, opiates, catecholamines, free radicals, calcium, nitric oxide and reactive oxygen related to the protective effects start; G protein, phospholipase C, protein kinase A, tyrosine protein kinase and mitogen-activated protein kinase mediated protective effect, The protective effect of the play and the ATP-sensitive potassium channels, 5 'nucleosidase and adenosine transcription factor inducible nitric oxide synthase, cyclooxygenase-2, aldose reductase, anti-free radical enzymes such as heat shock protein-related. Although existing research has revealed some lung ischemic preconditioning protection mechanisms, but still can not fully explain the protective effect caused by lung ischemic preconditioning and effectively reversed ischemia-reperfusion injury. Lung ischemic preconditioning in the clinical studies carried out late ischemic preconditioning as a supplementary measure of major surgery can be safely and clever implementation. Proteomics technology provides a new tool for the study of the protective mechanism of ischemic preconditioning. For this reason, the study of surgical patients in the clinical proteomics technology and methods of ischemic preconditioning molecular mechanisms of the anti-human lung ischemia-reperfusion injury. First choose the surgery patients were classified as sham group (Sham group, S group), ischemia-reperfusion group (Ischemia-reperfusion group, I / R group) and ischemic preconditioning group (Ischemic preconditioning group IP group). I / R group experienced pure ischemia-reperfusion IP group in to be ischemic preconditioning before ischemia-reperfusion S groups always maintain the blood supply and ventilation in the postoperative charged specimens. Then step extraction prepared S group, I / R group and IP group lung tissue protein, Two-dimensional gel electrophoresis repeatability and resolution better than those of the S group, I / R group and IP group lung tissue protein proteome. Dimensional electrophoresis profiles of the three groups of lung tissue proteins PDQuest software analysis and comparison, to draw more than four times the 20 differentially expressed protein spots using MALDI-TOF-MS mass spectrometry analysis of differentially expressed proteins for MALDI-TOF- MS peptide mass fingerprint database search identified 17 differentially expressed proteins. Finally, in order to verify the comparative proteomics research results, using the Western blot technique to detect the expression of some differences in the expression level of the protein in the lung tissue of the IP group and I / R group, consistent with the results of its results and comparative proteomics research. This study establish the S group, on the basis of two-dimensional electrophoresis map of the I / R group and IP group lung tissue protein, using mass spectrometry analysis combined with database search identified a total of 17 significantly differentially expressed proteins, these proteins according to the functions can be divided into eight categories, i.e. metabolism-related enzymes, antioxidants, ferritin, calcium binding proteins, molecular chaperones, cytoskeletal proteins, cell proliferation associated protein, as well as signal transduction proteins. Some of these proteins with spontaneous anti-ischemia-reperfusion injury, some proteins, such as HSP27 and of Cu / ZnSOD related to anti-active effect of ischemia-reperfusion injury of ischemic preconditioning, there are some protein and ischemic preconditioning against missing blood reperfusion injury related to the stabilizing effect. The research results to reveal ischemic preconditioning lung protection mechanisms, as well as provide a scientific basis for looking for ways to reversal of ischemia reperfusion injury.

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