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Effects of Rosuvastatin on Expression of NF-Kappa B and Interleukin-6 in Rats with Acute Myocardial Infarction

Author: YangShenXian
Tutor: WanDaGuo
School: Zhengzhou University
Course: Internal Medicine
Keywords: Rosuvastatin nuclear factor kappa B interleukin-6 inflammation rat
CLC: R542.22
Type: Master's thesis
Year: 2011
Downloads: 73
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Abstract

ObjectiveThe majority of the studies have shown that ventricular remodeling was found after acute myocardial infarction(AMI),and inflammatory cytokines in cardiac muscular tissue like interleukin 6 (IL-6),IL-1 and TNF-αexpression became more and the activity of nuclear factor kappa B (NF-κB) increased. The activated NF-κB was a heterodimer of p50 and p65,which were two factors of NF-KB/Rel family and had the ability of combining with target gene enhancer to promote the transcription.The NF-κB pathway played the critical role in transportation of cell information and transcription of manifold inflammatory factors.In other words,the expression of inflammatory cytokines would be affected effectually by interventing this pathway. A great deal of research indicated that statins had cardiovascular protective effects including anti-inflammatory effect beyond lowing the lipid, but the mechanism of anti-inflammatory wasn’t known yet.In this experiment,we modeled rats with AMI which was intervented by rosuvastatin(ROS),and then examined the changes of cardiac muscle adjacent to non infarcted zone after acute myocardial infarction as well as NF-κB and IL-6 expression,so as to explore the function of ROS in anti-inflammatory effect,and provide experimental basis for clinical treatment of AMI with ROS and ameliorating ventricular remodeling.Methods AMI model was generated by ligation of the left anterior descending(LAD) comnary artery in Wistar rats. All rats were divided into two groups randomly,15 in AMI group and 15 in ROS group.Then generated sham operation group with 10 rats which were tested with pierced but not ligated LAD. Each rat in ROS group was administrated orally with 10mg/(kg.d) while the others were 2ml normal saline. All rats were executed 4 weeks later.Then the pathological cardiac muscular tissue was observed after HE section staining on cardiac muscle tissue adjacent to non infarcted zone. Besides, the expression of NF-κB and IL-6 in other tissues were examined with immunohistochemical staining and RT-PCR.Results1. Survival situation.Both in AMI group and sham group ten rats survived while eleven did in ROS group.2. Overview of heart sample.Ventricular wall of AMI group was thinner than that of ROS group, collapsed and had congestion and edema.Compared with AMI group,cardiac tissues arrayed more tidily, rupture of cardiac tissues fibre less, fibrosis lighter, and the reaction of inflammatory cell was milder in the ROS group.3. No obvious expression of NF-κB and IL-6 were found in sham group. In AMI group, both mRNA expression and protein production of these cytokines were markedly higher than those in sham group(P<0.05). Significant reduction of mRNA expression and protein production of NF-κB and IL-6 were observed in ROS group, compared with those in AMI group (P<0.05), NF-κB and IL-6 were positively correlated (r=0.78-0.86,P<0.05).Conclusion1. Rosuvastatin has the effects on anti-inflammatory of myocardial infarction, improving ventricular remodeling and benifit for heart.2. Rosuvastatin can control the expression of NF-κB and IL-6, which are positively correlated.So we have the hypothesis that statins could enter into cytoplasm to intervene all factors stimulating the activity of NF-κB. Furthermore,they could reduce the inflammatory expression and their subsequent influence. That will provide experimental basis for clinical treatment of AMI using statins.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Myocardial diseases > Myocardial infarction
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