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The Therapeutic Efficacy and Potential Mechanisms of TSM on Atherosclerosis in Rats

Author: HuChen
Tutor: BianHuiMin
School: Nanjing University of Traditional Chinese Medicine
Course: Pharmacology
Keywords: Atherosclerosis Tongsaimai Tablet Inflammatory cytokines Angiotensin II
CLC: R285.5
Type: Master's thesis
Year: 2009
Downloads: 83
Quote: 0
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Abstract


The purpose of vascular endothelial cell damage is initiating atherosclerosis (Atherosclorosis, AS) links, hyperlipidemia, hypertension is the most important risk factors to cause the formation of AS. Lipid metabolism disorders, vascular endothelial injury, peroxide system disorders, expression of inflammatory cytokines enhance constitute of AS, the whole process of development. Therefore, the observation of drug intervention on different aspects of the AS process, study its mechanism of action. The experiment by rat AS model, given TSM treatment, observed changes in aortic morphology, detection hematology indicators and the expression of inflammatory cytokines in the cells, and to explore the mechanism of of TSM anti AS. Methods Healthy male Wistar rats, the control group normal feeding, the rest of the group a high fat diet and oral administration of VD 3 Copy rats AS model. After six weeks, according to lipid levels will model rats stratified randomly divided into four groups and orally administered therapy: the TSM the high-dose group (12.44g/kg.d), TSM low dose group (6.22g/kg.d ), simvastatin group (0.003g/kg.d), model group. At the same time, the model group and blank group given volume of 0.5% CMC-Na. Eight weeks after the administration, the number of blood testing CEC, serum lipids (TC, TG, HDL, LDL), CRP content; plasma MDA and SOD and Ang Ⅱ content; immunohistochemical assay NF-κB, MCP-1 CD40, CD40L, MMP-9, TIMP-1 expression of inflammatory cytokines in aortic cells; aortas, respectively, to the naked eye, light and electron microscopy morphology changes. Results 1, Tongsaimai piece of atherosclerosis rat artery morphology (1) naked eye and Oil Red O staining: rat model of arterial intima rough visible greyish yellow striped fatty streak, arterial poor flexibility, staining seen after the wall of the aorta significantly raised red stained plaque was heavier streak, basement membrane coloring; TSM can reduce the pathological changes. (2) HE stained light microscope: rat aortic intima of the control group, in the film, the outer membrane are visible layers of normal structure. Model group arterial intimal thickening, edema lesions fiber cells on the surface; TSM can improve arterial pathological structures. (3) transmission electron microscopy: the complete blank the rat artery walls EC morphology basic, internal elastic lamina legible. Rat model of EC severely damaged the internal elastic lamina thickness is uneven and there is an interruption, the organelles increased lipid; TSM can reduce endothelial cell damage, improve the internal elastic lamina structure to reduce lipid organelles. Piece of Tongsaimai atherosclerosis serum lipids and peroxide system (1) the impact of the number of CEC: TSM low doses can significantly reduce AS rat peripheral blood in the number of CEC. (2) effects on blood lipids: TSM can significantly reduce AS serum TC, TG, LDL content increased HDL levels. (3) the impact of MDA and SOD: TSM can be significantly increased the AS rat plasma SOD activity, decreased MDA content (P <0.05). 3 the piece of Tongsaimai atherosclerosis rat inflammatory cytokines TSM can reduce MCP-1, NF-κB, CD40, CD40L, of MMP-9/TIMP-1 in in AS rats arterial cells strongly positive expression weakly positive expression and expression. TSM low doses can significantly reduce serum CRP content (P <0.05); 4, Tongsaimai piece atherosclerosis angiotensin II TSM can significantly reduce the content of Ang Ⅱ in rat plasma (P <0.01) . Conclusion 1 TSM for experimental rat carotid artery atherosclerosis has a better therapeutic effect; TSM can improve serum lipid metabolism disorders, and enhance the body's antioxidant capacity, reduce inflammation, thereby protecting the VEC inhibit SMC proliferation, stable atheroma the AS treatment.

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