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The Control Study Of The Effects Of Pitavastatin On Rats With Acute Myocardial Infarction

Posted on:2009-10-04Degree:MasterType:Thesis
Country:ChinaCandidate:D D DongFull Text:PDF
GTID:2144360245484781Subject:Internal Medicine
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Objectives: This study is to investigate the effects of pitavastatin and atorvastatin on interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) in rats of Acute Myocardial Infarction, and compare the differences between two drugs of statins. Myocardial infarction is a severe type of coronary heart disease (CHD), closely correlated with the unstableness of atherosclerotic plaques。After acute myocardial infarction, the infiltration of polymorph nuclear and the expression of cytokines were increased. The injury of myocardium is related with the interaction of polymorph nuclear, vascular endothelial cell and myocardial cell. And plasma cytokines play a role of alteration and decoration. In China, the attack rate of hyperlipidemia is endless going up. But the rate of detection, therapy and being up to standard are all very low. There are a great of reason for this result, and one of them is never using the efficient drugs. 3 - Hydroxyl - 3 - methylgulutaryl coenzymeA reductase, statins, has been widely prescribed in patients with hyperlipidimia. What's more, it is reported that except for lipid-lowering, statins have been shown to exert additional beneficial, so-called pleiotropic effects. Such pleiotropic effects include improvement of endothelial dysfunction, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory responses, and stabilization of atherosclerotic plaques.This study is to investigate the changes of IL-6, TNF-αin rat of different models to discuss the long-term preventive use of pitavastatin and atorvastatin in protect injured myocardium and its possible mechanisms, as well as the differences between two drugs of statins, so that the statins can be better used in clini -cal therapies.Materials and Methods: 99 male Wister rats (250-300g ), were randomly divided into four groups: (1)Sham group (sham, n=15): normal saline 2ml/d ,after 4 weeks, open breast, no ligation of left anterior descending coronary artery (LAD). (2)AMI group (AMI, n=21): normal saline 2ml/d, after 4 weeks, open breast, ligation of LAD. (3) Preventive group (Pitava, n=21): gavages with pitavastatin 0.36mg/kg/d, after 4 weeks, ligation of LAD. (4)positive-compare group(atorva组,n=21): gavages with atorvastatin 3.6mg/kg/d, after 4 weeks, ligation of LAD. Every group was subdivided into three units: post myocardial infarction for 0.5hour, 1hours and 1.5 hours. After assuring the success of surgical procedures according to the standards, we respectively collected 4ml blood to discern the levels of IL-6, TNF-α. All data are presented as mean±SEM. The statistical significance of the changes in different models were analyzed by SAS statistics software. A value of P<0.05 was accepted as statistically significant. Results:1 The concentration change of plasma cholesterolThere were of unremarkable difference in weight and plasma cholesterol concentration (1.76±0.56 vs. 1.79±0.22 vs. 1.85±0.18 vs. 1.72±0.30mmol/l,P>0.05).2 Concentration changes of IL-6 in serumOver time, the levels of IL-6 were increased in the same group. In AMI group, Pitava group and Atorva group, the levels of IL-6 showed statistically different at three time points(P<0.05):(91.949±10.013)vs.(126.224±25.455)vs.(217.141±10.673)pg/ml,(67.360±6.836)vs(.85.247±2.153)vs(.111.667±3.403)pg/ml,(68.851±0.112)vs(.83.464±2.267)vs.(112.254±5.912)pg/ml. At the same time point, the relationship between levels of IL-6 is AMI group>(Pitava group, Atorva group)>Sham group, and the differences are statistically(P<0.05); but there're no statistically differences between Pitava group and Atorva group.3 Concentration changes of TNF-αin serumOver time, the levels of TNF-αwere increased in the same group. In AMI group, Pitava group and Atorva group, the levels of TNF-αshowed statistically different at three time points(P<0.05): (0.6877±0.0505)vs.(0.9537±0.0200)vs.(1.1123±0.1716)ng/ml,(0.5350±0.0461)vs(.0.7618±0.0113)vs. ( 0.8816±0.1217 ) ng/ml ,( 0.5270±0.0221 ) vs.(0.7751±0.0144)vs(.0.8799±0.0011)ng/ml. At the same time point, the relationship between levels of TNF-αis AMI group> ( Pitava group, Atorva group ) > Sham group, and the differences are statistically(P<0.05); but there're no statistically differences between Pitava group and Atorva group.Conclusions:1 Via investigate the changes of IL-6, TNF-αlevel in different groups at different time points, present study shows that the severity of injured myocardium is correlated with the expression of former cytokines. With the time changing, the myocardial injury was accelerated.2 Compared with AMI group, the concentrations of IL-6 and TNF-αis lower in Pitava and Atorva groups, and the difference is statistically significance (P<0.05). It showed that through long-term preventive prescribing pitavastatin and atorvastatin will reduce the injury of post myocardial infarction, which is independent of lipid-lowering effect and put forward a theoretical foundation for the prescription of statins in clinical therapies.3 In Pitava and Atorva groups,there're no statistically differences in levels of IL-6 and TNF-αat the same time points. It shows that in lowering the levels of IL-6 and TNF-α, their effects are commensurate.
Keywords/Search Tags:myocardial infarction, pitavastatin, atorvastatin, IL-6, TNF-α
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