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The Protective Effect Of MIR-499 On Myocardial Infarction Model In Pigs

Posted on:2016-05-24Degree:MasterType:Thesis
Country:ChinaCandidate:Y J GuoFull Text:PDF
GTID:2284330470975139Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
With high morbidity and mortality, acute myocardial infarction(acute myocardial infarction, AMI), a severer clinical cardiovascular emergency,is one of the major diseases harmful to human’s health. So far, our country has entered an aging society, the incidence of AMI was gradually increased,reaching 45 ~ 55/100000, and its age of onset showed younger trend. In recent years, with the extensive development of intravenous thrombolytic therapy and percutaneous coronary intervention(PCI), the therapy of AMI still has not been absolutely solved though the treatment and prognosis of AMI patients are significantly improved, AMI patient’s health and quality of life are still in enormous threat. Therefore, there is an urgent need to develop new technology and explore a more effective method in early diagnosis and treatment of AMI. As a kind of endogenous non-coding small RNA molecule, small RNA(miRNA) is expressed in the normal and patients with various of diseases, it not only participates in regulating multiple signaling pathways, but also exists in the peripheral blood stably.MIRNA- 499 is one of the members with high cardiac specificity in miRNA family. Studies have shown that miR-499 participates in the inhibition of myocardial cell apoptosis caused by cardiac ischemia and hypoxia, it has a protective effect on myocardial cells and also can enhance the quality of hearts damaged by myocardial infarction and recover its function. Therefore, taking mi RNAs as a new target for cure of AMI and developing relative drugs with clinical application value will provide a broad prospect for the treatment of AMI.Our study was to block the left anterior descending coronary artery(LAD) by OTW angioplasty balloon to establish a swine model of AMI. It divided the 9 Chinese mini pig into three groups: sham-operated group(group S,n=3)、model group(group M,n=3)、miR-499 analog processing group(group MA,n=3). The pigs were given different post-processing methods accordingly: for the sham-operated group, it only placed the angioplasty balloon on 1/3 place of LAD, do not blocking the coronary arteries; For the model group, it filled the angioplasty balloon with contrast media for 30 seconds, then pumped out the contrast media for 30seconds(five cycles), after 1 hour′s ischemia and then restoring reperfusion;For the miR-499 analog processing group, miR-499 analog was injected via center cavity of OTW angioplasty balloon based on the model group and then restoring reperfusion.Our study observed the filling time of contrast media by frame counting, watched the variation in cardiac hemodynamics, viewed the changes of QRS wave and ST segment. We also detected the myocardial necrosis markers such as the active concentration of Creatine kinase enzyme(CK-MB) protein and the concentration of cardiac troponin I(c-TnI),to discuss the protection effect of miR-499 to the ischemic myocardial cells damaged by pig myocardiac infarction.The results showed that, the model group and miR-499 analog processing group had an obvious cardiac injury after ischemia compared with the sham-operated group. The filling time of contrast media was longer, ST segments elevated obviously, the concentration of CK-MB and c-TnI also obviously rised. There was a significant difference(P<0.05).Compared with the model group, the degree of cardiac injury was light relatively. All the indexes were improved to some degrees. It can decrease the filling time of contrast media and ST segments elevation range, the concentration of CK-MB and c-TnI were also reduced, there was a significant difference( P<0.05).No obvious change in cardiac hemodynamic index statistics.The above results suggest that miR- 499 can reduce the degree of myocardial ischemia、itigate damage of ischemia myocardial cells,it has certain protective effect to the pig myocardial infarction model.
Keywords/Search Tags:miR-499, acute myocardial infarction, CK-MB, c-TnI, ischemia-reperfusion, pig
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