N-acetyl-L-cysteine On Rabbit Atherosclerotic Model The Impact Of Matrix Metalloproteinases

Experiment with my background:Atherosclerotic cardiovascular disease is a common one, the latest research results show that atherosclerosis is a chronic inflammatory reaction, IL-1, TNF-a, such as a series of pro-inflammatory cytokines involved in the process, and low-density lipoprotein (LDL) formed by oxidative modification of low-density lipoprotein (ox-LDL) is the key to this process-induced inflammatory factors.Macrophage cells in atherosclerotic plaque formation and the develop- ment process has played an important role. Role of pro-inflammatory cytokines, endothelial cell adhesion molecule expression and secretion, chemical chemokines, monocyte migration to vascular endothelium, and differentiate into macrophages. ox-LDL oxidative stress as a material is to promote atherosclerosis and the development of important factors.Ox-LDL can be scavenger receptor macrophage unlimited intake, which leads to macrophage lipid cholesterol in a large number of particle accumulation, finally formation of foam cells, foam cells Atherosclerosis are classic cells, in the whole Atherosclerosis process of foam cells secrete matrix metalloproteinase (MMPs), the degradation of the basement membrane to smooth muscle cell migration, and promote the progress of atherosclerosisMMPs belong to the Zn2 +dependent protease family, are now known to have 23 family members, specific degradation of extracellular matrix, plaque rupture often occurre in the fibrous cap shoulder, its fibrous cap is the thinnest, collagen content and - glucan less fibrous cap bear the tension, anti-poor rupture, which is one of the important factors of matrix metalloproteinases (MMPs) expression and activation.MMPs could be divided into six categories: (1) collagenase (Collage- nases): decompositionⅠ,Ⅱ,Ⅲinterstitial collagen and extracellular matrix molecules. (2) gelatinase (Gelatinases): divided into MMP-2 and MMP-9, decomposition of collagen degradation products, gelatin, interstitial collagen,Ⅴ,Ⅶ,Ⅸ,Ⅹcollagen, elastic protein, laminin protein, protein and polysaccharide fibronectin. (3) Dissolution of mesenchymal (Stromelysins): In addition to the degradation of the substrate, MMP-3, MMP-10, a degradation of cartilage and other polysaccharide protein activation of MMPs the initial factor.(4) membrane-type matrix metallo proteinases (MT-MMPs): fibrin degradation gel, laminin, Bolivia and even protein of chondroitin sulfate polysaccharide protein and the cell surface adhesion can be activated metalloproteinases precursors. (5) matrix lytic enzyme (Matrilysins): Apart from the extracellular matrix, MMP-7 can be dealt with before the tumor necrosis factor -α, and E-cadherin protein epithelial cells, etc. (6) other MMPs.MMP main artery in the membrane from the patch of smooth muscle cells and mononuclear macrophages, and by inflammatory cytokines that increase the expression of pressure, secretion and activation.The matrix metallopr- oteinases - 2,9 (MMP– 2,9) with the extracellular matrix degradati- on strong.Ⅳof the basement membrane and collagen fibers atherosclerotic plaque are the important component of the cap, MMP - 2,9 promote degradation of smooth muscle cells in the membrane to the endometrium migration, and accelerate the process of atherosclerosis. ox-LDL can be increased through of matrix metalloproteinases (MMPs) and matrix-degrading enzyme (stromelysins) activity, and promote thrombosis.NAC as mucus solvent has been used from the beginning of 1962, and has achieved good results. Its mechanism is considered because of its free sulfhydryl to cracking mucus in the disulfide-glycoprotein molecules, thereby reducing the viscosity of sputum. In recent years, many research results show that NAC as an important antioxidant, which has a direct and indirect antiox- idant role of reactive oxygen species, can interfere with the generation of free radical generation which has been removed, and a series of signal transduction and gene expression play an important role in the same time, NAC also have an impact on cell apoptosis in tumor transplantation , and other roles. Some of the toxic substances in the detoxification process, NAC also shows a good role. Jian-Hua Cui, etc. [5] study shows that NAC can inhibit atherosclerosis in the induction of macrophage foam cells in the expression of MMP-2 and MMP-9.Methods:This study further explore the N-acetyl-L-cysteine and the antioxidant role of MMP-2,9 inhibition of mRNA, thus the prevention and treatment of coronary heart disease in a new way.Experimental in vitro applications of this artery balloon catheter injuryed rabbit carotid artery after high-fat diet for the establishment of animal models, and N-acetyl-L-cysteine to 15 mg / kg group of 30 mg / kg group intervention, the use of SDS-page-Zymography detected in the serum matrix metallopro- teinase-using ELISA method to detect after four weeks and eight weeks in the serum of ox-LDL, the plaque samples from doing RT-PCR, observation of N-acetylcysteine on MMP-2,,9mRNA expression.Result: (1) NAC (15mg/kg) in the treatment group compared the control group pro-MMP-2 decreased 44.6% (P <0.05), MMP-2 decreased 54.0% (P <0.05), and pro-MMP-9 decreased 45.2% (P <0.05), NAC (30mg/kg) in the treatment group compared the control group pro-MMP-2 decreased 58.7% (P <0.05), MMP-2 dropped 63.76% (P <0.05), and pro-MMP-9 decreased 49.8%.(2) 4 weeks after NAC (15mg/kg) in the treatment group compared the control group ox-LDL decreased 6.2% (P <0.05), NAC (30mg/kg) in the treatment group compared the control group ox-LDL decreased 13.2% (P <0.05 ), eight weeks after the NAC (15mg/kg) in the treatment group compared the control group ox-LDL decreased 10.7% (P <0.05), NAC (30mg/kg) in the treatment group compared the control group ox-LDL decreased 15.7% (P <0.05). (3) NAC15mg/kg Group N-acetylcysteine on MMP-2, MMP-9 mRNA expression and secretion almost no impact (P> 0.05); NAC30mg/kg N-acetyl group ammonia cysteamine acid can inhibit MMP-2 and MMP-9 mRNA expression (P <0.05).Conclusions: N-acetyl-L-cysteine can inhibit the formation of ox-LDL, inhibit matrix metalloproteinase-mRNA expression and serum levels of MMPs, which can plaque stability.