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N-acetylcysteine Inhibits Oxidized LDL, Metalloproteinases-9 Sercretion And Apoptosis In Atherosclerosis

Posted on:2011-11-01Degree:MasterType:Thesis
Country:ChinaCandidate:Z X LiFull Text:PDF
GTID:2144360305954523Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Atherosclerosis is a complex disease, of which, oxidative stress is atherosclerosis risk factors, and influence the formation of atherosclerosis and the various stages of development, which can cause proteins, lipids, nucleic acids substances too oxidation, caused by abnormal cell structure and function and induce a variety of oxidative stress response, activation of atherosclerotic plaques in a variety of cellular components to promote the occurrence and development of atherosclerosis. Thus, antioxidant therapy is imperative. This study was designed to find an effective antioxidant therapy drugs, can have the effective and efficient anti-atherosclerosis effect. Past my mentor led research team had done a considerable part of the NAC study to prove that reduce in vitro levels of MMPs within the foam cells; in rabbits fed high-fat diet, NAC also plays intervention atherosclerosis The role, which could reduce intimal thickness and luminal stenosis, ox-LDL levels and MMPs levels, and reduce the mRNA expression of MMPs. And some studies prove that:in vitro experiments, the exposure to high ox-LDL in the environment of cultured cells, the number of apoptotic cells was higher than that of normal cells, while the experimental results showed that:the same exposure to high ox-LDL environment, Applications NAC group compared with the number of apoptosis does not apply Group has reduced, but the results showed that the number of NAC cell apoptosis compared with normal cells, no significant difference. Comprehensive information on past research that has the NAC as an antioxidant drug, could play an antioxidant role, this study aims to confirm that different experimental models, different experimental methods, different targets under observation, NAC's anti-atherosclerotic hardening effect.In this study, select 8-week-old male Apoe knockout (Apoe-/-) mice were studied, a total of 10, with an average weight of 20g. Were randomly divided into high-fat diet group (control group), and NAC interfere with treatment group (experimental group), two groups of mice were treated with high-fat diet for 60 days, NAC intervention group administered a dose of 300mg/kg, according to body weight of mice in each of the on the required dose, administered through drinking water bottle means, and to ensure that set up a daily dose of drug intake. Modeling 60 days, to give a 24-hour fasting mice, pick the eye blood, placed in test tubes containing EDTA-specific biochemical tests carried out centrifugation, separated plasma, placed in-80℃to save. Off mice were sacrificed, rapid separation of mouse aortic arch, placed in 4% paraformaldehyde fixed 36-48 hours to carry out dehydration, transparent, Baptist wax, embedding operation, access to paraffin-embedded specimens. By in situ immunofluorescence staining method for the determination artery intima-mouse MMP-9 levels of office, the application pro-inherent characteristics of the nuclear fluorescent stain to observe the NAC in atherosclerosis during the course of apoptosis; in serological testing, the choice of ELISA method was determined to assess the plasma MMP-9 in mice with ox-LDL levels; artery atherosclerotic plaques in the general morphological study using hematoxylin-eosin (HE) staining method, histological specimens of atherosclerotic lesions in general shape.In the general model of atherosclerosis, the visual plaque morphology:NAC experimental groups of mice interfere with atherosclerotic plaque volume and plaque distribution area than those of high-fat diet group reduced; HE stained specimens, NAC group of foam cell volume compared with the control group significantly reduced the plaque volume in the foam cells and plaque lipid core size significantly reduced compared with control group; by in situ fluorescent staining method for the determination of arterial intima expression of MMP-9 positive cells, NAC The positive cells than the control group (P<0.05), there is statistical significance determined by the number of apoptotic cells, NAC group the number of apoptotic cells than the control group (P<0.05), there is statistical significance; NAC group compared with the control group, can reduce plasma ox-LDL and MMP-9 levels (both P <0.05), both statistically significant.Through this experiment, we conclude that:NAC can reduce the number of atherosclerotic plaque, plaque distribution area, reducing the number of foam cells, reducing the volume of foam cells in plaques, plaque lipid core volume; NAC can reduce the arterial endometrial expression of MMP-9 in the number of positive cells; NAC can reduce atherosclerotic plaques in the number of apoptotic cells; NAC can reduce plasma ox-LDL and MMP-9 levels. This experiment further confirmed the NAC's anti-atherosclerosis effect of NAC as an anti-atherosclerosis drugs used clinically to provide an experimental basis.
Keywords/Search Tags:N-acetylcysteine, atherosclerosis, matrix metalloproteinase -9, oxidized low-density lipoprotein, apoptosis
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