Dissertation
Dissertation > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Vascular disease > Artery disease

The Effect and Mechanism of Simvastatin to the Atherosclerotic Rats

Author ShangKe
Tutor YuanZhanQun
School Nanchang University
Course Internal Medicine
Keywords Matrix metalloproteinase-12 Matrix metalloproteinase-2 Aortic Atherosclerosis Simvastatin
CLC R543.5
Type Master's thesis
Year 2007
Downloads 203
Quotes 2
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Background: atherosclerosis (Atherosclerosis, AS) is based on the formation of atherosclerotic plaques is characterized by large and medium-sized artery intima, middle arterial wall is weak, bureaucratic tone narrow, complicated by thrombosis, bleeding, ulcers, aneurysm formation, and a series of concurrent disease, leading to cardiovascular and cerebrovascular disease, serious harm to human health. Control study of autopsy and angiographic results found that 70% of patients with acute myocardial infarction occurred 50% of coronary stenosis lt; Unstable plaque rupture and secondary thrombosis is the main reason to trigger an acute coronary syndrome, and therefore prevention artery atherosclerosis formation and stability of atherosclerotic plaques become the treatment of arterial atherosclerosis key. Unstable plaque pathology characterized: extracellular lipid pool, fibrous cap is weak, at the junction of more lipid-rich macrophages in plaque and normal endometrium, plaque lipid Deposition and clearance, inflammatory injury and repair, stromal hyperplasia and degradation throughout the plaque, the whole process of development and remodeling, and biological characteristics and natural processes affect plaque. Matrix metalloproteinases (Matrix metalloproteinases, MMPs) involved in vascular remodeling, the stability of the atherosclerotic plaque. Matrix metalloproteinase activity largely determines the thickness and collagen content of the fibrous cap. Macrophage metalloelastase (Macrophage metalloelastase) MMP-12, and gelatinase (gelatinases from) MMP-2 is of particular concern, since MMP-12 expression by macrophages and vascular smooth muscle cells, and MMP-2 by the vascular smooth muscle cells and leukocyte expression, both of which can degrade the basement membrane and collagen components. Normal blood vessel wall smooth muscle cells are mainly located in the film, wrapping around the basement membrane. Basement membrane with smooth muscle cell contact can be maintained smooth muscle cells in contraction genotype, to limit its movement. Both of which can effectively degrade the basement membrane, cell migration road sweeping, involved in the migration of smooth muscle cells and endothelial hyperplasia. Objective: To study simvastatin on matrix metalloproteinase -12 (MMP-12), matrix metalloproteinase -2 (MMP-2) in the expression and activity of rat aortic atherosclerosis, and to explore its anti-atherogenic hardening of the possible mechanisms. Methods: 30 male Sprague-Dawley rats were randomly divided into three groups: control group, model group, treatment group, using the method of high-fat diet with intraperitoneal injection of vitamin D3 rat atherosclerosis model, feeding eight weeks. End of the experiment, each group was detected serum lipids, structural changes observed aortic tissue, immune staining of the aortic wall matrix metalloproteinase -12 (MMP-12), the expression of matrix metalloproteinase -2 (MMP-2) application gelatin zymography (Zymography) detection of aortic wall matrix metalloproteinase (MMP-2) activity. Results: Compared with model group, the therapeutic serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) levels the most obvious significant difference (P lt; 0.05), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) both levels (P lt; 0.01). Significantly reduce the treatment group rat aortic atherosclerosis in the aortic wall MMP-12, MMP-2 expression compared with the model group was significantly lower (P lt; 0.01), MMP-2 vitality compared with the model group was significantly lower (P lt ; 0.01). Conclusion: Simvastatin anti-atherosclerotic role with lipid-lowering, may also be related to the inhibition of MMP-12, MMP-2 expression and activity. Inhibition of MMP-12, MMP-2 expression and activity may be one of the mechanisms of simvastatin anti-atherosclerotic hardening. This conclusion has important implications for exploring the pathogenesis of atherosclerosis and anti-atherosclerotic role outside clarify statin lipid-lowering.

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