Influence Of Grape Seed Proanthocyanidin Extract On Matrix Metalloproteinase Of Experimental Atherosclersis

BackgroundAtherosclerosis is a kind of disease threatening the life and health of human beings, and it is the pathological basis of cardiovascular and cerebrovascular diseases. So it is significant to investigate the mechanism and the treatment of atherosclerosis to prevent and cure cardiovascular and cerebrovascular diseases. Studies have shown that the forming process of atherosclerosis is also the remodeling course of extracellular matrix. The matrix metalloproteinase(MMP) degrades extracellular matrix and plays an important role in extracellular matrix remodeling. MMP content rises, the activation of MMP is strengthened, and that brings about an advance in atherosclerosis. Grape seed proanthocyanidin extract is a kind of polyphenol compound extracted from grape seeds and it has potent antioxidant activity, capable of scavenging free radicals with low toxicity. Studies recently discover that GSPE has the efficacy of antiatherogenesis, but the function mechanism has not been totally expounded yet. We set up experimental atherosclerosis model through feeding rabbits with rich cholesterol diet and offer them GSPE at the same time, and we observe the effects of GSPE on matrix metalloproteinase of experimental atherosclerosis rabbits and try to explore the mechanism of antiatherogenesis of GSPE.Objective(1)To investigate the anti-atherogenic effect and the possible mechanism of GSPE through the animal model of experimental atherosclerosis.(2)To observe the effect of grape seed proanthocyanidin extract on the serum matrix metalloproteinase of rabbits. Methods24 male New Zealand rabbits were randomized into three groups with 8 rabbits in each group. The control group were fed with standard diet. The cholesterol group were fed with standard diet containing 1% cholesterol. The GSPE group were fed with standard diet containing 1% GSPE plus 1% cholesterol. All the rabbits were fed for twelve weeks. Blood samples were drawn just on the day before the experiment and at the fourth, the eighth and the twelfth weekend of the experiment. The blood samples were analyzed for . matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9(MMP-9). All the rabbits were sacrificed at the twelfth weekend, and aorta of the rabbits were excised for the morphological observation and immunohistochemical examination. Serum MMP-2 and MMP-9 were measured using a commercially available MMP-2 and MMP-9 ELISA kit. Aorta samples were observed through optical microscope, and the expression of MMP-2 and MMP-9 were observed in the thoracic aortic tissue using immunohistochemistry technique. One-way-anova of SPSS 10.0 software was used to evaluate the differences between the cholesterol group and the grape seed proanthocyanidin extract group. ResultsCompared with the cholesterol group,(1)The serum MMP-2 and MMP-9 contents were lowered markedly by dietary grape seed proanthocyanidin extract.(2) The extent and severity of atherosclerosis of the grape seed proanthocyanidin extract group were less than those of the cholesterol group, and the stability of the atherosclerotic plaque of the GSPE group was strengthened bygrape seed proanthocyanidin extract. ConclusionGSPE has the efficacy of antiatherogenesis, which is associated with reducing the expression of matrix metalloproteinase.